Polypharmacy Guidance

Acknowledgements
It has been a pleasure to chair the development of this Polypharmacy Guidance 2015 and work with
a team that are committed to improving outcomes for patients. This document has been produced
by the collaborative efforts of the clinicians from multidisciplinary backgrounds that make up the
Model of Care Group from across Scotland. They are already delivering on polypharmacy reviews to
improve appropriate prescribing and patient safety. In addition the Data, Indicators and Evaluation
Group have provided the tools and data to help target patients. There has also been the
development of national indicators that are available for boards to use at practice level for peer
review and improvement. We have been supported by a team of Medicines information Pharmacists
from across Scotland under the leadership of Janice Watt and Melinda Cuthbert who have worked to
provide the data to support the numbers needed to treat (NNT) tables, and are listed below. Finally I
would like to thank Tobias Dreischulte, Simon Hurding and Jason Cormack for the support that they
have provided in terms of the structure and presentation of the document, making it far more user
friendly. We are also currently working with colleagues in NES to produce a mobile app for clinicians
to use when undertaking the reviews.
Model of Care Group
Alpana Mair, Deputy Chief Pharmaceutical Officer, Scottish Government (Chair)
Martin Wilson, Consultant, NHS Highland
Miles Witham, Consultant, NHS Tayside
Graeme McPhee, Consultant, NHS Greater Glasgow and Clyde
Kathryn Wood, Principal Clinical Pharmacist (Geriatric Medicine), NHS Tayside
Tobias Dreischulte, Research Pharmacist, NHS Tayside
Janice Watt, Lead Pharmacist Medicines Information Services, NHS Greater Glasgow and Clyde
Melinda Cuthbert, Lead Pharmacist Lothian Medicines Information Service, NHS Lothian
Neil Houston, GP, NHS Forth Valley
Thomas Ross, Lead Pharmacist (South & Mid Highland Operational Unit), NHS Highland
Stewart Mercer, Professor of General Practice, Glasgow University
Data, Indicators and Evaluation group
Alpana Mair, Deputy Chief Pharmaceutical Officer, Scottish Government (Chair)
Vicky Elliott, Principal Information Analyst, NHS National Services Scotland
Steve Kendrick, Information Consultant, NHS National Services Scotland
Bruce Guthrie, Professor of General Practice, Dundee University
Rachel Porteous, Senior Information Analyst, NHS National Services Scotland
Gavin McColl, Principal Analyst, NHS National Services Scotland
Nils Michael, Economic Advisor, Scottish Government
Medicines Information pharmacists
Janice Watt, Lead Pharmacist Medicines Information Services, NHS Greater Glasgow and Clyde
Melinda Cuthbert, Lead Pharmacist Lothian Medicines Information Service, NHS Lothian
Tracy Duff, Senior Pharmacist, NHS Lothian
Karen Harkness, Principal Pharmacist (Clinical Effectiveness), NHS Tayside
Tracy Love, Principal Pharmacist (Medicines Information), NHS Ayrshire and Arran
Elaine McIvor, Medicines Information Pharmacist, NHS Greater Glasgow and Clyde
Elaine Sheridan, Medicines Information Pharmacist, NHS Grampian
Alpana Mair, MRPharmS, IP, FFRPS
Acting Chief Pharmaceutical Officer
2
Foreword
The care of patients with multiple medical conditions is one of the greatest challenges now faced by
healthcare providers. To date the vast majority of medical research, guidelines and contractual
agreements have dealt with single targets for single disease states, whereas in reality many patients
have multiple chronic conditions, requiring multiple treatments. The resulting polypharmacy (use of
multiple medicines) can be both appropriate and inappropriate and the key healthcare aim for
individual patients is to ensure the on-going safe and effective use of their multiple medicines.
Research into the management of patients with multiple medical conditions is in relative infancy.
Despite this there is the requirement to provide guidance to both patients and healthcare providers
based on the best evidence to date.
We are delighted to present the Polypharmacy Guidance 2015, which builds on and refines the
previous guidance from 2012. The ‘7-steps’ is a clear structure for the medicines review process,
which is centred around the individual adult patient, and presented in a number of forms to facilitate
its use across a range of healthcare settings. An electronic version is to be produced as an ‘App’.
Further clarity is provided for important definitions such as appropriate and inappropriate
polypharmacy, and what is meant by the term frailty. The methodology to identify potentially frail
patients on potentially inappropriate polypharmacy has been developed since 2012, and case studies
are presented to demonstrate the importance of a holistic review of the individual patient when
trying to get the best outcomes from medicines. Of particular note is the further work that has been
done on the relative efficacy of medicines. Medicines Information resource has developed the use of
the relative numbers needed to treat, for key therapeutic areas, in order to help inform patients of
the potential benefits and risks of continuing treatment.
The Appropriate prescribing for patients and polypharmacy guidance CEL 36 (2012) required that
NHS Boards would have plans in place to identify priority patients with potentially inappropriate
polypharmacy and to review those patients at greatest risk. It is understood that this work is
underway. With the publication of this Polypharmacy Guidance 2015 the requirement now is that the
boards will build on the foundational work of the last three years and focus resource on accelerating
the capacity of polypharmacy reviews in order to further increase the benefit to patients.
Alpana Mair
Chief Pharmaceutical Officer
(Acting)
Aileen Keel
Chief Medical Officer
(Acting)
Jason Leitch
Clinical Director
Healthcare Quality and Strategy
If using any content from this document, please acknowledge the Scottish Government Model of
Care Polypharmacy Working Group
When referencing this document, please use the following format:
Scottish Government Model of Care Polypharmacy Working Group. Polypharmacy Guidance (2nd
edition). March 2015. Scottish Government
Cover image courtesy of Piyachok Thawornmat at FreeDigitalPhotos.net
3
Contents
1. General Principles......................................................................................................................................... 5
The review process ............................................................................................................................................ 9
1.1
The ‘7-steps’ approach to medication review ................................................................................. 9
1.2
Reviewing medication need and effectiveness ............................................................................. 16
1.2.1
Assessing the need for preventative treatment in patients with shortened life
expectancy/frailty ................................................................................................................................... 16
1.2.2
1.3
Understanding numbers needed to treat (NNT) ................................................................... 16
Tool to assess cumulative risk of drug toxicity and ADRs ............................................................... 31
2. Case studies: The ‘7 steps’ approach in action ........................................................................................... 32
Case 1: Multimorbidity without frailty ........................................................................................................ 32
Case 2: Frailty without overt multimorbidity .............................................................................................. 35
Case 3: Frailty with Multimorbidity ............................................................................................................. 38
Case 4: Care home resident with multiple morbidity .................................................................................. 41
3. Hot topics: Further background reading .................................................................................................... 43
3.1
Anticholinergics.............................................................................................................................. 43
3.2
Medication & The Risk of Falls in the Older Person ...................................................................... 46
3.3
Stopping antipsychotics in patients with dementia ..................................................................... 48
3.4
Stopping benzodiazepines and z-drugs ......................................................................................... 49
3.5
Management of constipation ........................................................................................................ 52
3.6
Management of blood glucose control- effects of intensifying control ....................................... 53
Appendix A: General Medication Review leaflet ............................................................................................. 54
Appendix B: Sick Day Rules: Information for healthcare professionals and patients ...................................... 55
Appendix C: NNT and the Methodology for NNT used .................................................................................... 57
Appendix D: Health Economics Analysis of Polypharmacy reviews ................................................................. 59
Appendix E: Indicators and monitoring............................................................................................................ 62
4
1. General Principles
Medication is by far the most common form of medical intervention for many acute and chronic
conditions. Drug therapy can be highly effective in preventing disease or slowing disease progression,
with guidelines for single diseases recommending the use of a variety of evidence based drug
treatments. However, there is often a mismatch between prescribing guidelines for specific medical
conditions and the range of clinical complexity found in individual adults. For complex patients with:
(1) multiple conditions; (2) frailty; (3) a dominant condition (e.g. dementia) or (4) approaching the
end of their lives, the implementation of the sum of evidence based recommendations may: not be
rational; increase the risk of adverse drug events and misaligned with the patient’s preferences.
Why review polypharmacy?
The term polypharmacy itself just means “many medications” and has often been defined to be
present when a patient takes five or more medications. However, it is important to note that
polypharmacy is not necessarily a bad thing. For example, secondary prevention of myocardial
infarction often already requires the use of four different classes of drugs (antiplatelets, statins, ACE
inhibitor, beta blocker). Polypharmacy can be both rational and required. It is therefore crucial to
distinguish appropriate from inappropriate polypharmacy.
Inappropriate polypharmacy is present, when one or more drugs are prescribed that are not or no
longer needed, either because: (a) there is no evidence based indication, the indication has expired
or the dose is unnecessarily high; (b) one or more medicines fail to achieve the therapeutic objectives
they are intended to achieve; (c) one, or the combination of several drugs cause inacceptable
adverse drug reactions (ADRs), or put the patient at an unacceptably high risk of such ADRs, or
because (d) the patient is not willing or able to take one or more medicines as intended.
Appropriate polypharmacy is present, when: (a) all drugs are prescribed for the purpose of achieving
specific therapeutic objectives that have been agreed with the patient; (b) therapeutic objectives are
actually being achieved or there is a reasonable chance they will be achieved in the future; (c) drug
therapy has been optimised to minimise the risk of ADRs and (d) the patient is motivated and able to
take all medicines as intended.
Which patients should be targeted?
In the absence of definitive evidence on which patients are most likely to benefit from a holistic
review of their medication, the following two groups of patients will be identified as potential
candidates for medication review:
A. All patients in care homes age 50+ regardless of the number of medicines that they are on
B. Patients who are:
o Aged 75 and over, (progressing to 65-74 as resources allow)
o On 10 or more medicines, one of which is a high risk medication
o and with a SPARRA score in the range 40 to 60%
The numbers in these groups by NHS Board are shown in Tables 1a and 1b. It should be noted that
the two groups overlap, so many patients will be in both groups A and B. (Of the patients included in
Table 1a as resident in a care home, 6861 aged 75 and over also appear in Table 1b and 7251 aged 65
and over also appear in Table 1b.)
Where there are large numbers using the above process, additional prioritisation may be needed and
we suggest focussing on patients who meet one or more of the following criteria for complexity:
(1) Multiple conditions: In Scotland, over half of all people with chronic conditions have two or more
conditions. In other words, it is now more common to have two or more long term conditions than
only one.1 Most people aged 65 years or older have two or more long term conditions and the
majority of people aged 75 years or older have three or more. Although there is a clear link between
1
Barnett K, Mercer SW, Norbury M, Watt G, Wyke S, Guthrie B. Epidemiology of multimorbidity and
implications for health care, research, and medical education: a cross-sectional study. The
Lancet;380(9836):37-43
5
getting older and the likelihood of having long term conditions it would be wrong to see this as a
problem purely associated with older age. In fact quite the reverse is true: the majority of people
with two or more chronic conditions are younger than 65. Many of these adults will be attempting to
balance the needs and demands of work and family. Deprivation is also strongly linked with
multimorbidity, adding in all the complexity this brings to an adult’s life.
(2) Frailty: There is an increasing recognition that older age itself should not be a specific focus.
Instead, a more functional individualised approach is recommended. To this end the term ‘frailty’ is
becoming the preferred term. A recent Best Practice statement from the British Geriatrics Society
notes that:
Frailty is a clinically recognised state of increased vulnerability. It results from ageing
associated with a decline in the body’s physical and psychological reserves. Frailty varies in
its severity and individuals should not be labelled as being frail or not frail but simply that
they have frailty. The degree of frailty of an individual is not static; it naturally varies over
time and can be made better and worse.
Adults who are frail lack the reserve to deal with adverse events. Even minor physical and mental
stresses can have a big impact on health. Prescribing in this group needs particular attention as
guidelines are unlikely to take the presence or absence of frailty into account when making
recommendations. This places frail adults at particular risk of: adverse drug reactions: drug to drug
interactions or rapid deterioration if necessary medication is not optimised.
(3) Dominant condition: Standard guidelines will recommend treatment for that single condition
rather than in the context of other, often multiple conditions. Certain conditions are recognised to
‘dominate’ the picture for the adult both practically and prognostically. Of these perhaps dementia is
the best example where its impact affects and informs decisions for every other condition.
(4) Approaching the end of their lives: Adults of any age, approaching the end of their life due to any
cause, are likely to have different prescribing needs, and risk versus benefit discussions should differ
from healthy adults with long life spans.
Table 1a. All SPARRAA patients aged 50 and over in care home.
1st September 2014. All risk scores.
Age 50+
NHS Board
NHS Ayrshire & Arran
NHS Borders
NHS Dumfries & Galloway
NHS Fife
NHS Forth Valley
NHS Grampian
NHS Greater Glasgow & Clyde
NHS Highland
NHS Lanarkshire
NHS Lothian
NHS Orkney
NHS Shetland
NHS Tayside
NHS Western Isles
Total
Number in a care homeD
2,567
555
979
2,285
1,610
3,132
7,228
1,969
3,033
4,233
87
93
2,825
169
30,765
6
Table 1b. Patients in SPARRAA on 1st September 2014 with a risk score of 40-60% who were dispensed items from 10 or more BNF sectionsB
Age 75+
NHS board
NHS Ayrshire & Arran
NHS Borders
NHS Dumfries & Galloway
NHS Fife
NHS Forth Valley
NHS Grampian
NHS Greater Glasgow & Clyde
NHS Highland
NHS Lanarkshire
NHS Lothian
NHS Orkney
NHS Shetland
NHS Tayside
NHS Western Isles
Total
Number of
patients
3,670
943
1,360
2,755
1,950
3,448
10,400
2,305
4,521
5,449
144
170
3,206
264
40,585
Number
with high
risk
C
medicines
3,592
925
1,328
2,672
1,911
3,353
10,147
2,248
4,421
5,298
140
168
3,127
263
39,593
Number in
a care
D
home
645
109
210
568
329
643
1,637
372
655
990
18
25
625
35
6,861
Age 65+
Number
with high
risk
medicines
and in a
care home
621
104
204
548
319
614
1,582
360
642
953
17
25
597
35
6,621
Number
with
E
dementia
558
140
206
649
311
592
1,593
328
769
1,107
30
37
538
40
6,898
Number
of
patients
4,634
1,163
1,693
3,399
2,447
4,207
13,234
2,879
5,875
6,638
200
215
3,826
321
50,731
Number
with high
risk
C
medicines
4,534
1,133
1,649
3,293
2,401
4,090
12,904
2,799
5,742
6,455
194
212
3,729
318
49,453
Number in
a care
D
home
680
115
219
596
344
688
1,729
405
699
1,039
21
26
650
40
7,251
Number
with high
risk
medicines
and in a
care home
655
110
212
574
334
658
1,668
392
684
998
20
26
622
40
6,993
Number
with
E
dementia
594
149
227
695
329
644
1,699
356
835
1,186
34
38
559
46
7,391
A
SPARRA Version 3 estimates the risk of emergency admission in the next 12 months for approximately 3.6m individuals aged 16 years of age and older.
For the September 2014 release, this is the risk of emergency admission in the period 1st September 2014 to 31st August 2015.
B
The number of different BNF sections from which a patient's drugs were prescribed and dispensed. SPARRA Version 3 uses the most recent 12 months prescribing data
available prior to the start of the risk year.
C
Defined as medications in any of the following BNF Sections: 2.1, 2.2, 2.4, 2.5, 2.8, 2.9, 4.1, 4.2, 4.3 and 10.1.
D
Identified by a CHI institution code of 93 or 98.
Evidence of dementia has been determined either by prescribing history (dispensed items within BNF Section 4.11) or previous inpatient admission to hospital
where diagnosis at discharge includes ICD10 codes (F00-F03, F051); and ICD9 codes (2900, 2901, 2902, 2904, 2908, 2909).
Requesting SPARRA listings of patients who may be candidates for medication review.
E
7
How does this guideline aim to help?
This second edition of the Scottish national guideline on polypharmacy is a major upgrade to the
information presented in the last edition and is part of ongoing work aimed at providing more
detailed information that is accurate, understandable, and is useful in practice to both prescribers
and patients.
1. By providing a clear structure for a drug review that is centred around the individual adult.
Clinicians are encouraged to see the adult under review in a holistic manner and include nonpharmacological solutions as well as medication ones.
2. Focus on knowledge and understanding. Large sections of this guideline are set aside to provide
information to both clinicians and patients. As a result both are empowered to advise, discuss and
make decisions on what to take and why.
3. Worked examples presented as case studies. The four case studies are intended to demonstrate
the importance of a holistic review of the individual patient when trying to get the best outcomes
from medicines. This includes considering the benefits and risks of treatment in the context of
multiple co-morbidities, individual social circumstances and the patient’s overall wellbeing. The case
studies also illustrate the importance of careful medical assessment in formulating a diagnosis and
problem list.
4. Medication safety. Medicines are implicated in 5 - 17 per cent of hospital admissions, of which
approximately half are considered potentially preventable. The majority are due to well-known
adverse effects of commonly prescribed drugs. There is a clear and steady increase in the number of
patients admitted to hospital with adverse drug effects.2 Information and guidance is given on some
of the most common medication safety issues.
5. Drug efficacy and applicability table (Number Needed To Treat (NNT) Chart). Medicines
Information Pharmacists across Scotland have collaborated to produce a table that summarises what
information is currently available regarding the efficacy of a number of commonly prescribed
medications. Being aware of the NNT of different therapies for the same disorder can help to inform
rational and patient-centred therapy. The table includes information on the characteristics of adults
studied in those trials. This is important as estimating an individual patient’s risk in conjunction with
the NNT can guide the prescriber and patient in determining the value of a drug intervention where
symptomatic relief is not the aim.
Who is this guideline targeted at?
This guidance aims to support those carrying out comprehensive face-to-face medication reviews
(defined as Level 3 reviews) with patients and where appropriate carers and welfare proxies (e.g.
those with power of attorney regarding health related issues). It also contains much information that
patients will find useful.
2
Co-morbidity and repeat admission to hospital for adverse drug reactions in older adults: retrospective cohort
study Zhang, Min et al. BMJ 2009; 338: a2752
8
The review process
1.1
The ‘7-steps’ approach to medication review
The following seven steps are intended as a guide to structure the review process. An overview of
aspects to cover in each step is presented in table 2A. Table 2B lists drugs and drug classes that may
be relevant under each step and links to table 2C, where more detailed information on each drug
(class) is provided. Table 2C is organised by BNF chapter, which will facilitate access to drug specific
information. Where relevant, tables 2A to 2C provide links to section 1.2 (background information for
reviewing medication need and effectiveness) and section 1.3 (Tool to assess cumulative risk of drug
toxicity and ADRs).
Step 1: Identify aims and objectives of drug therapy. Before embarking on a clinical medication
review it is helpful to establish the aims and objectives of drug therapy on the basis of the
information available, i.e. patient demographics, medical and drug history, laboratory markers, social
situation. Based on this information, likely treatment objectives can often be identified, and will
require agreement with the patient (see step 7).
Step 2: Identify essential drug therapy. A rational first step of the medication review is to separate
the list of drugs the patient is currently taking into those that are essential and should usually not be
stopped from those that could potentially be stopped. Essential drugs in this respect are those that
have a replacement function or may cause rapid symptomatic decline or loss of disease control if
stopped.
Step 3: Does the patient take unnecessary drug therapy? For the remaining drugs, it should be
verified that each has a function in achieving the above defined therapeutic objectives and whether
their use is supported by a sufficient up to date evidence base. In addition to stopping drug therapy
with expired indications, the continued need for prophylactic treatments in patients with a short life
expectancy should be considered.
Step 4: Are therapeutic objectives being achieved? The next step is to check whether the remaining
drugs are the most effective for the indication they are used for and whether they are actually
achieving what they are intended to achieve. If this is not the case, the possibility of patient nonadherence should be investigated as a potential explanation. Otherwise, the need for intensifying
doses or adding or replacing drugs may also be considered.
Step 5: Is the patient at risk of ADRs or suffers actual ADRs? The presence of ADRs can sometimes
be identified from laboratory data (e.g. hypokalaemia from diuretic use), or the patient reports such
symptoms. However, ADR identification often requires a more pro-active approach of identifying
ADR risks (including drug-drug and drug-disease interactions, but also the patient’s ability to selfmedicate) and asking the patient specific questions (e.g. about the presence of anticholinergic
symptoms, dizziness or drowsiness).
Step 6: Is drug therapy cost-effective? Opportunities for cost minimisation should be explored, but
changing drugs for cost reasons should only be considered if effectiveness, safety or adherence are
not comprised.
Step 7: Is the patient willing and able to take drug therapy as intended? Assessment of adherence
has been mentioned in steps 4 and 5 as a way to explain drug therapy failure or identify drug therapy
risks, but this steps aims at optimising the drug regimen so that adherence is as easy as possible. In
order to maximise their involvement and cooperation, patients should be explicitly asked what they
hope to achieve from drug therapy and be empowered to make decisions regarding effectiveness
versus safety as well as symptom control versus longevity.
9
Table 2a: An overview of the ‘7-steps’ with Links to section of greater detail
Domain
Aims
Steps
1.
2.
Identify
objectives of
drug therapy
Identify
essential drug
therapy
Need
3.
Effectiveness
Safety
Costeffectiveness
Adherence/
Patient
centeredness
4.
Does the
patient take
unnecessary
drug therapy?
Are
therapeutic
objectives
being
achieved?
5.
Does the
patient have
ADR or is at
risk of ADRs?
6.
Is drug
therapy costeffective?
7.
Is the patient
willing and
able to take
drug therapy
as intended?
Process
Review diagnoses and identify therapeutic objectives with
respect to:
 Management of existing health problems
 Prevention of future health problems
Identify essential drugs (not to be stopped without
specialist advice)
 Drugs that have essential replacement functions (e.g.
thyroxine)
 Drugs to prevent rapid symptomatic decline (e.g. drugs
for Parkinson’s disease, heart failure)
Identify and review the (continued) need for drugs
 with temporary indications
 with higher than usual maintenance doses
 with limited benefit in general for the indication they
are used for
 with limited benefit in the patient under review (see
Drug efficacy & applicability (NNT) table)
Identify the need for adding/intensifying drug therapy in
order to achieve therapeutic objectives
 to achieve symptom control
 to achieve biochemical/clinical targets
 to prevent disease progression/exacerbation
Identify patient safety risks by checking for
 drug-disease interactions
 drug-drug interactions (see ADR table)
 robustness of monitoring mechanisms for high-risk drugs
 drug-drug and drug-disease interactions
 risk of accidental overdosing
Identify adverse drug effects by checking for
 specific symptoms/laboratory markers (e.g.
hypokalaemia)
 cumulative adverse drug effects (see ADR table)
 drugs that may be used to treat ADRs caused by other
drugs
Identify unnecessarily costly drug therapy by
 Consider more cost-effective alternatives (but balance
against effectiveness, safety, convenience)
Identify risks to patient non-adherence by considering
 Is the medicine in a form that the patient can take?
 Is the dosing schedule convenient?
 Is the patient able to take medicines as intended?
 Might the patient benefit from the Chronic Medication
Service (CMS)?
 Is the patient’s pharmacist informed of changes to
regimen?
Ensure drug therapy changes are tailored to patient
preferences by
 Discuss with the patient/carer/welfare proxy
therapeutic objectives and treatment priorities
 Decide with the patient/carer/welfare proxies what
medicines have an effect of sufficient magnitude to
consider continuation or discontinuation
10
Table 2b: Drug groups for the ‘7-steps’ with Links to greater detail by BNF chapter
Essential drug therapy – Only consider stopping following specialist advice
Discuss with expert before stopping
o Diuretics - in LVSD (7)
o ACE inhibitors - in LVSD (17)
o Steroids
o Heart rate controlling drugs
Discuss with expert before altering
o Anti-epileptics
o Antidepressant
o Antipsychotic
o Mood stabilisers
o Amiodarone
o DMARDs
o Thyroid hormones
Potentially unnecessary drug therapy
Check for expired indication
Check for valid indication
benefit versus risk
o PPI(1) /H2 blocker (2)
o Laxatives (3)
o Antispasmodics (4)
o Oral steroid (22, 36)
o Hypnotics/anxiolytics (24)
o H1 blockers (29)
o Metoclopramide (28)
o Antibacterials (oral/topical) (32)
o Antifungals (oral/topical) (33)
o Sodium/potassium suppl. (44, 45)
o Iron supplements (44)
o Vitamin suppl. (44)
o Calcium/Vitamin D (44)
o Sip feeds (44)
o NSAIDs (46)
o Drops, ointments, sprays etc. (49)
o Anticoagulant (5)
o Anticoagulant + antiplatelet (6)
o Aspirin (6)
o Dipyridamole (6)
o Diuretics (7)
o Digoxin (9)
o Peripheral vasodilators (10)
o Quinine (11)
o Antiarrhythmics (13)
o Theophylline (21)
o Antipsychotics (25)
o Tricyclic antidepressants (27)
o Opioids (30)
o Levodopa
o Nitrofurantoin (32)
o Alpha-blockers (39)
o Finasteride (40)
o Antimuscarinics (urological) (41)
o Cytotoxics/immunosuppressant
(43)
o Muscle relaxants (47)
o Antianginals (12)
o BP control (15)
o Statins (14)
o Inhaled steroids (20)
o Dementia drugs (26)
o Bisphosphonates (37)
o HbA1c control (34)
o Female hormones (42)
o DMARDs (48)
(see Drug efficacy &
applicability (NNT) table)
Effectiveness
If therapeutic objectives are not
achieved: Consider intensifying
existing drug therapy
o Laxative - Constipation (3)
o Antihypertensives - BP control (15)
o Antidiabetics - HbA1c control (34)
o Warfarin - INR control
o Rate limiting drugs - Heart rate?
o Respiratory drugs – Symptoms?
o Pain control
For patients with the following potential indications:
Consider if patient would benefit from the specified drug therapy
o (see Drug efficacy & applicability (NNT) table)
o CHD - Antithrombotic, statins, ACEI/ARB, beta blocker
o Previous stroke/TIA - Antithrombotic, statin, ACEI/ARB
o LVSD - Diuretic, ACEI/ARB, beta blocker
o AF - Antithrombotic, rate control
o DMT2 - Metformin
o High fracture risk - Bone protection
Safety
Drugs poorly tolerated in frail adults
See Gold National Framework on
frailty
o Antipsychotics (incl.
phenothiazines)
o NSAIDs (46)
o Digoxin (doses ≥ 250 mcg) (9)
o Benzodiazipines (24)
o Anticholinergics (incl. TCAs) (27)
o Combination analgesics
High-risk clinical scenarios
See ADR table
See “Sick day rules” cards
o Metformin + dehydration
o ACEI/ARBs + dehydration
o Diuretics + dehydration
o NSAIDs + dehydration
o NSAID + ACEI/ARB +
diuretic
o NSAID + CKD
o
o
o
o
o
o
o
o
o Branded products
o >1 strength of same drug
o Unsynchronised dispensing
intervals (28 or 56 day supplies)
NSAID + age >75 (without PPI)
NSAID + history of peptic ulcer
NSAID + antithrombotic
NSAID + CHF
Glitazone + CHF
TCA + CHF
Warfarin + macrolide/quinolone
≥2 anticholinergics (see
Anticholinergics)
Cost-effectiveness
Check for
o Costly formulations ( dispersible)
o Costly unlicensed ‘specials’
Adherence/patient centeredness
Check self-administration (cognitive)
o Warfarin/New
o Analgesics
OAC’s
o Methotrexate
o Anticipatory care
meds eg COPD
Check self-administration (technical)
o Inhalers
o Any other devices
o Eye drops
o Bisphosphonates/calcium
11
Table 2c: Information on targeted drugs (by BNF) with Links to section of greater detail
The table below briefly provides the rationale behind targeting each drug or drug group as well as
some practical guidance. It may be used as a reference while preparing for a face to face medication
review. The list is an amalgamation of existing collections of explicit medication assessment tools
(including START/STOPP, DQIP and others), but it is important to note that no list can be
comprehensive and the reviewer’s clinical judgement and experience continue to be essential in
tailoring the advice given to the needs of an individual patient and to identify any additional
medication related problems.
BNF Chapter 1: Gastrointestinal system
1
PPIs
o If long term treatment is necessary, ensure doses don’t exceed usual maintenance
doses
o CAUTION: Clostridium difficile, osteoporosis, hypomagnesaemia
2
H2 blockers
o CAUTION: Anticholinergic ADRs! See Anticholinergics, See ADR table
3
Laxatives
o CAUTION: Vicious cycle of fluid loss > hypokalaemia > constipation
 If >1 laxative: Do not stop abruptly. Reduce stimulant first and monitor effect
 See advice here on non-pharmacological options:
4
Antispasmodi
cs
o Rarely effective; rarely indicated long term
o CAUTION: Anticholinergic side effects
BNF Chapter 2: Cardiovascular system
5
Anticoagulan
ts
o Check for expired indications (e.g. temporary loss of mobility that has now resolved)
o Much more effective for stroke prevention in AF than antiplatelets - See NNT table
o CAUTION: Bleeding events. Avoid combinations of anticoagulants, antiplatelets,
NSAIDs
o Ensure patient adherence to dosing/monitoring regimen
 If patient is unfit for warfarin for cognitive reasons (NOACs may not be indicated
either)
○
6
Antiplatelets
o NOTE: Antiplatelets are no longer indicated for 1 prevention of CHD
o Aspirin plus clopidogrel indicated for a maximum of 12 months after ACS only
o CAUTION: Bleeding events. Avoid combinations of anticoagulants, antiplatelets,
NSAIDs
 Consider PPI in those with additional GI risk factors (but avoid clopidogrel+
[es]omeprazole)
○
o Consider antiplatelets as part of 2 prevention strategy after CVD events - See NNT
table
○
 First line antiplatelet for 2 stroke prevention is clopidogrel (rather than
dipyridamole)
7
Diuretic
o Usually essential for symptom control in heart failure
o Note: Not indicated for dependent ankle oedema (consider medication causes, e.g.
CCBs)
o CAUTION: AKI and electrolyte disturbances
o Advise patient to stop during intercurrent illness; Is U&E monitoring robust?
8
Spironolacto
ne
o CAUTION: Hyperkalaemia. Risk factors include: CKD (CI if eGFR<30ml/min), dose
>25mg/d, co-treatment with ACEI/ARBs, amiloride, triamterene, potassium
supplements
9
Digoxin
o CAUTION: Toxicity! Risk factors are: CKD, dose>125mcg/d, poor adherence,
hypokalaemia, drug-drug interactions
10 Periph.
vasodil.
o Rarely effective; rarely indicated long term
11 Quinine
o Use short term only when nocturnal leg cramps cause regular disruption of sleep
o Review effectiveness regularly
o CAUTION: Thrombocytopenia, blindness, deafness
12 Antianginals
o Consider reducing antianginal treatment if mobility has decreased
12
o CAUTION: Hypotension (Consider use of other BP lowering drugs; avoid combination
with sildenafil)
13 Antiarrhythm
ic
Amiodarone
o In AF: Rate control usually has better benefit/risk balance than rhythm control
14 Statins
o Recommended for 1 and 2 prevention in patients at high risk of CVD See NNT table
o CAUTION: Rhabdomyolysis: Check interactions (e.g. fibrates, dihydropyridines,
antiinfectives)
o Consider need for and intensity of treatment in light of life expectancy and ADR risk
See NNT table
15 BP lowering
drugs
o Limited evidence supporting tight BP control in the older frail group
o Individualise BP targets for primary and secondary prevention of CVD guidelines
o Consider need for and intensity of treatment in light of CVD risk life expectancy and
ADR risk See NNT table
16 Beta blockers
o Usually essential for rate and angina control in CHD and CHF (and often in AF)
o BNF recommends up-titration of BB doses in CHF to evidence based target doses
o CAUTION: Bradycardia in combination with diltiazem/verapamil, digoxin and
amiodarone
17 ACEI/ARBs
o Usually essential for symptom control in CHF. For other potential benefits: See NNT
table
o BNF recommends up-titration of ACEI/ARB doses in CHF to evidence based doses
o CAUTION: AKI. Avoid combination with NSAIDs and advise pt to stop when at risk of
dehydration
18 CCBs
o CAUTION: Constipation, ankle oedema
o Dihydropyridines - CAUTION: Reflex tachycardia/cardiodepression: Avoid nifedipine
in CHD/CHF
o Diltiazem/verapamil - CAUTION: Bradycardia in comb. with BBs or digoxin (digoxin
levels ↑↑)
19 Spironolacto
ne
o Recommended in moderate to severe CHF: See NNT table
o CAUTION: Overdosing. Maintenance should be max 200mg/day
o CAUTION: Thyroid complications. Ensure monitoring tests are being done
o Monitor LFTs
○
○
o CAUTION: Hyperkalaemia. Risk factors: CKD, combination with ACEI/ARB,
triamterene, amiloride
o CAUTION: AKI. Avoid combination with NSAIDs and advise pt to stop when at risk of
dehydration
BNF Chapter 3: Respiratory system
20 Inhalers
o Assess symptom control (NICE recommends : Ask specifically about frequency of
inhaler use)
o Assess inhaler technique and adherence to dosing schedule
o Also see Respiratory Prescribing Strategy
21 Theophylline
o Monotherapy in COPD is not appropriate - safer, more effective alternatives are
available
o CAUTION: Toxicity (tachycardia, CNS excitation)
o Avoid combination with macrolides and quinolones
22 Steroids
o Long term oral use for respiratory disease rarely indicated.
 Withdraw gradually if: use >3 weeks, >40mg prednisolone/d
 When stepping down use of steroid inhalers: Reduce dose slowly (by 50% every
3 months)
o CAUTION: Osteoporotic fractures: Consider bone protection if long term treatment
necessary
o Ensure use of steroids aligned with COPD GOLD guideline
23 Antihistamin
o Rarely indicated long term
st
es (1
o CAUTION: Anticholinergic ADRs! See Anticholinergics
generation)
BNF Chapter 4: Central nervous system and psychotropic medication
24 Hypnotics
o CAUTION: Risk of falls/fractures, confusion(!), memory impairment
See section 3.4 for specific information on benzodiazepines and Z drug withdrawal
and
13
anxiolytics
25 Antipsychotic
s
26 Antidementia
drugs
27 Antidepressa
nt
Tricyclics
SSRIs
28 Metoclopramide
29 Antihistamin
es
30 Opioids
and insomnia guidelines here
 CAUTION: Risk of dependency
o CAUTION: Risk of stroke and death in elderly patients with dementia! See
Antipsychotics
o CAUTION: Anticholinergic ADRs for phenothiazines (eg chlorpromazine)! See
Anticholinergics
o CAUTION: Worsening of Parkinson’s disease (specialist advice is recommended)
o Formally assess benefit:
 If MMSE score is ≥10: Continue if drug benefits global, functional or behavioural
symptoms
 If MMSE <10, only continue if drug helps with behaviour (NICE recommends
memantine)
o Confirm need (First episode: Treat for 6-9 months; Second + episode: Treat for ≥2
years)
o CAUTION: Anticholinergic ADRs! See Anticholinergics SSRIs are better tolerated in
the elderly
o CAUTION: Risk of GI bleeding may be increased
o Avoid combination with MAOIs because of the risk of serotonine syndrome
o Now only licensed for use for a max of 5 days (does not apply to off label use in
palliative care)
o CAUTION: Worsening of Parkinson’s disease (domperidone more suitable but note
contra-indications in cardiac disease and severe liver disease)
o Rarely indicated long term for treatment of vertigo
o CAUTION: Anticholinergic ADRs! See Anticholinergics
o Assess effectiveness/choice (is pain neuropathic or otherwise not responsive to
opiates? e.g. chronic back pain, widespread pain, fibromyalgia, medically unexplained
symptoms)
 See : Chronic Pain Scotland
 SIGN 136 Management of Chronic Pain
 SIGN 106; Control of Pain in Adults With Cancer
o CAUTION: Constipation. Use laxatives
o CAUTION: Cognitive impairment and respiratory depression, dependency,
and suppression of sex hormones
oimmunosuppression
CAUTION: overdosing
 Ensure patient is aware of minimum interval between doses and max daily dose
 Avoid >1 paracetamol product
 Consider dose reduction where low body weight, renal or hepatic impairment
32 Antiepileptics
o Assess effectiveness/dose if used for pain management: Is pain neuropathic, use
DN4 or LANSS to aid diagnosis. Titrate dose up to assess efficacy. Limited evidence
for musculoskeletal pain / Fibromyalgia) See chronic pain Scotland and SIGN 136
Management of Chronic Pain
o CAUTION: Dizziness, blurred vision and sedation. Reduced dose in CKD. Check renal
function
BNF Chapter 5: Infections
32 Antibacterials
o Evidence of no benefit for treating asymptomatic bacteriuria (ASB) in diabetes or
(oral)
older adults
o Review use of long term antibiotics for recurrent UTI (every 6 months)
o Lack of evidence for antibiotic use in preventing catheter associated ASB
Nitrofurantoi
o CAUTION: Pulmonary/renal ADRs; avoid in renal impairment; contraindicated if
n
GFR<30ml/min
33 Antifungals
o CAUTION: Risk of arrhythmia and HF exacerbation with azole antifungals
BNF Chapter 6: Endocrine system
34 Antidiabetics
o Indicated to control symptoms of hyperglycaemia (metformin is first line in DMT2)
o Note: It takes years for the benefit (mostly microvascular risk) of tight HbA1C control
to accrue. Establish individual HbA1c targets balancing any benefits vs
hypoglycaemia risk See NNT table
31 Paracetamol
35 Metformin
Sulfonylureas
Glitazones
36 Steroids
o
diabetes
prescribing
strategyAvoid if eGFR < 30ml/min. Stop when at risk of
o See
CAUTION:
Risk
of lactic acidosis.
dehydration
o CAUTION: Hypoglycaemia: Active metabolites can accumulate when renal function is
impaired
o Avoid in patients with heart failure
o Rarely indicated for long term use. Consider dose reduction/withdrawal where
14
37 Bisphosphonates
possible
 If treatment
is >12
weeks,
monitor
forfor
osteoporosis
(DXA
scan)
o Consider
need forduration
treatment
in light
of risk
factors
osteoporotic
fractures:
previous osteoporotic fragility fracture, parental history of hip fracture, alcohol
intake ≥4 units/d, rheumatoid arthritis, oral steroids, BMI<22 kg/m2), ankylosing
spondylitis, Crohn’s disease, prolonged immobility, untreated menopause. See NNT
table
o Check patient’s ability and willingness to take bisphosphonates (and calcium) as
instructed
 There are no current guidelines for bisphosphonate holidays/discontinuation in
the UK
 There is no evidence to guide monitoring after discontinuation of bisphosphonate
therapy
 Women who stop alendronate after 5 years rather than continuing for 10 years
show moderate decline in bone mineral density and a gradual rise in biochemical
markers but no high fracture risk except clinical vertebral fractures.
 Women at high fracture risk may benefit from continuing alendronate beyond 5
years but this should be a considered decision rather than automatic
3
continuation
BNF Chapter 7: Gynaecology and urinary-tract disorders
39 Alphao Generally not indicated if a patient has a long term catheter
blockers
40 Finasteride
o Generally not indicated if a patient has a long term catheter - discuss with urology
re: stopping
41 Antimuscarini
o Review continued need/effectiveness after 3-6 months
cs
o CAUTION: Anticholinergic ADRs (oxybutynin may decrease MMSE score in people w
dementia)
42 Female
o NOTE: There is no cardio-protective effect or cognitive protection in older women
o CAUTION: Carcinogenic potential in breast and endometrium
hormones
o Discuss with patient individual balance of benefits and risks
BNF Chapter 8- Malignant Disease and Immunosuppression
43 Cytotoxics
o Is treatment still consistent with treatment objectives? Refer to doctor who initiated
etc
treatment
BNF Chapter 9 - Nutrition & blood
44 Supplements
o Confirm continued need/effectiveness and set a stop/review date;
o Monitor weight
45 Potassium
o CAUTION: Hyperkalaemia. Risk factors: Use without stop/review date, CKD, cotreatment with ACEI/ARBs, spironolactone, amiloride, triamterene, trimethoprim)
BNF Chapter 10: Musculoskeletal and joint diseases
46 NSAIDs
o CAUTION: Gastro-intestinal ADRs (Risk factors: age>75, GI ulcer, antithrombotics,
steroids, SSRIs, high alcohol use)
 If NSAIDs are essential: Consider gastro-protection with a PPI in those with GI risk
factors
o CAUTION: Cardiovascular ADRs (Risk factors: CVD risk>20%, previous CVD events,
heart failure)
o CAUTION: Renal ADRs (Risk factors: age>65, on ACEI/ARBs and/or diuretics, CKD or
heart failure)
 If NSAIDs are essential: Monitor eGFR; advise patient to stop during intercurrent
illness
47 Skeletal
o Rarely indicated long term (except for patients with spacicity)
o CAUTION: Anticholinergic ADRs
muscle
relaxants
48 DMARDs
o Assess effectiveness and discuss any need for changes with secondary care specialist
Methotrexate
o CAUTION: Overdosing. Avoid preparations with different strength
o Ensure patient adherence to dosing/monitoring regimen
BNF Chapter 11 to 13 – Eye, skin, ear, nose & oropharynx
49 Drops, sprays
o Set a review/stop date for topical antibacterial/antifungal and sympathomimetic
Ointments
preparations
o Review need for preservative free eye drops (e.g. previous preservative toxicity)
15
1.2
Reviewing medication need and effectiveness
1.2.1 Assessing the need for preventative treatment in patients with shortened life
expectancy/frailty
Identifying patients with shortened life expectancy
We suggest that following guidance contained in the prognostic indicators guidance from the Gold
Standards Framework incorporated into the ‘Living Well/Dying Well’ strategy enables better
identification of patients who may need supportive/ palliative care. A full copy is available here.
Characteristics which can be used to identify patients with shortened life expectancy include:
1. Where the answer to the question ‘would you be surprised if this person were to die in the
next 6 to 12 months?’ is ‘no’
2. Where a patient with advanced disease is making a choice for comfort care rather than
‘curative’ treatment
3. Where help is required for multiple activities of daily living, either at home or in care home
due to:
a. advanced organ failure
b. multiple co-morbidity giving significant impairment in day to day function
c. advanced dementia
The Gold Standards Framework gives specific information as to what tends to indicate poor prognosis
in a number of conditions, for example frailty. The Supportive and Palliative Care Indicators Tool
(SPICT) is a further tool developed in Scotland that also gives a picture of adults where end of life
issues may need to be considered. It is available here.
Identifying frailty
Frailty is well defined as a ‘reduced ability to withstand illness without loss of function’. The Gold
Standards Framework defines this further as:
1. Multiple co-morbidities with signs of impairment in day to day functioning
2. Combination of at least three of:
a.
b.
c.
d.
e.
1.2.2
Weakness
Slow walking speed
Low physical activity
Weight loss
Self-reported exhaustion
Understanding numbers needed to treat (NNT)
The ‘number needed to treat’ (NNT) is a measure used in assessing the effectiveness of a particular
medication, often in relation to a reduction in risk over a period of time. The NNT is the average
number of patients who require to be treated for one to benefit compared with a control in a clinical
trial. It is defined as the inverse of the absolute risk reduction. So if treatment with a medicine for
one year reduces the death rate over five years from 5% to 1% (a very effective treatment), the
absolute risk reduction is 4% (5 minus 1), and the NNT is 100/4 =25.
In other words, the number needed to treat with that medicine for one year to prevent one death is
25. The ideal NNT is 1 where everyone improves with treatment. The higher the NNT, the less
effective is the treatment. There is always a need to consider:
16
 What is the outcome being avoided? Death is more significant than a vertebral fracture, but
different outcomes will be more or less significant to individual patients
 Over what period does the benefit accrue? Two drugs may have the same NNT to avoid one
death, but the drug that achieves that over 6 months is more effective than the drug which
takes 10 years. You can put NNTs on the same timescale by multiplying or dividing the NNT
appropriately, but there is an assumption that benefit accrues consistently over time (a not
unreasonable assumption, but one that is difficult to test)
 What are the TRUE costs of the drug? This will include monetary costs, but also costs
associated with treatment burden, and harm/side effects. A medicine might save the life of
one of the 25 people who take it, but if it led to all 25 suffering a debilitating side effect, its
costs may outweigh its benefits
NNTs are only estimates of average benefit, and it is rarely possible to know precisely what the likely
benefit will be in a particular patient. Clinicians and patients should also be aware of a degree of
‘uncertainty’ in the number since it is usually not possible to calculate valid confidence intervals
around NNTs.
‘Number needed to harm’ (NNH) is a related measure which is the average number of people
exposed to a medication for one person to suffer an adverse event. Again, a defined end point (e.g.
GI bleeding or renal failure) requires to be specified and confounders may require correction of the
raw data i.e. in very elderly patients the risk of particular side effects such as confusion and falls may
be higher than on average . In discussion, the overall benefit – risk ratio (NNT / NNH) requires to be
‘weighed’ in the individual patient and may vary considerably in people with polypharmacy
depending on absolute risk, life expectancy and vulnerability to adverse drug events.
Example:
The reference below illustrates that for benzodiazepines for night sedation NNT is 13 but the NNH is
6
Glass, J. et al. Sedative hypnotics in older people with insomnia: a meta-analysis of risks and
benefits. BMJ 2005; 331: 1169
Applicability of Trial Data to Individual Adults
Included in the Drug Efficacy chart is information on the trial population and the duration of the trial.
The closer an adult is in terms of their own characteristics and duration of treatment to the trial the
more likely the trial is to give a good estimate of what they can expect to obtain from the treatment.
Conversely the further away they are the less likely the information is to be applicable. This can work
in both directions and treatment could be either more or less effective.
An example would be the comparison between a ‘Frail’ and ‘Non – Frail’ adult. If two adults present
on the same medication and with the same range of diagnoses the answer to how effective their
medication would be in terms of both benefit and harm depends on their other attributes. One may
be functioning well and still working despite their ill health. The other may be more clearly nearing
the end of their life and in a phase of increasingly high dependence. The latter adult is unlikely to
have been represented (or even thought of) in a trial situation.
Adults approaching end of life have an increased risk of many events, so each individual event has a
higher Absolute Risk. This means that interventions may have a much lower NNT for that adult. This
should be balanced against the shorter time they have in life to obtain a benefit and the increased
risk that any harm, even small, may have a higher impact.
Efficacy data must only be considered as one aspect of the whole drug review process keeping in
mind particularly Steps 1 (objectives of treatment) and 7 (willingness for treatment) which consider
the Patient Centred goals and aims in the context of their life as a whole.
17
Drug Efficacy Chart
Medicine or
intervention
Comparator
Study
population
Outcome
Duration
of trial
No treatment
Patients with
hypertension
and age > 80yrs
Total mortality
2 years
Number
needed to
treat (NNT)
Annualised
number
NNT
333
666
Comments
HYPERTENSION
1 BP control
(<140/90mmHg)
High risk is defined as patients with a previous history of
stroke
Cardiovascular mortality and morbidity includes fatal MI and
non-fatal MI, sudden cardiac death, aneurysms, congestive
heart failure, fatal and non-fatal stroke and transient
ischaemic attacks
2 BP control
(<140/90mmHg)
3 BP control
(<140/90mmHg)
4 BP control
(<140/90mmHg)
No treatment
No treatment
No treatment
Patients with
hypertension
High risk and
greater than 80
years
Patients with
hypertension
age > 60yrs
Patients with
hypertension
High risk and >
60 years
Cardiovascular
mortality and
morbidity
Total mortality
2 years
35
70
2 years
333
666
Cardiovascular
mortality and
morbidity
Total mortality
2 years
16
32
4.5 years
83
374
Cardiovascular
mortality and
morbidity
Total mortality
4.5 years
23
104
4.5 years
33
149
Cardiovascular
mortality and
morbidity
4.5 years
9
41
Total mortality is death from all causes
NB the evidence base to support the NNT for impact on
mortality in the over 80’s is very limited
18
HEART FAILURE
5 ACE inhibitor
(ramipril
10mg/day)
6 ACE inhibitor
(enalapril 2.5 40mg/day (uptitrated as
tolerated)
Placebo
Placebo
Patients at
high-risk of
cardiovascular
disease without
LVSD or heart
failure
High-risk of CVD
defined as:
history of CHD,
stroke, PAD or
DM plus one
other CVD risk
factor (HTN,
elevated total
cholesterol, low
HDL, smoking or
microalbuminuria)
Prevent one
death (all cause)
Patients with
severe heart
failure
NYHA class IV
Prevent one
death (all cause)
Co-morbidities
included CHD,
previous MI ,
HTN and DM
3
60
months
54
270
Mean age of enrolled patients was 66 years. >50% of
patients had a history of MI
Ramipril reduced the risk of myocardial infarction, stroke,
coronary revascularisation and heart failure
There is no data to support ARBs for this indication
188 days
(mean
followup)
7
3
Mean age of patients was 70 years3
Symptomatic improvement was observed i.e. A significant
improvement in NYHA classification
NB Patient numbers in the study were low (n=253)
The Consensus Trial Study Group. Effects of enalapril on mortality in severe congestive heart failure. The New England Journal of Medicine. 1987; 316(23): 1429-1435
19
7 ACE inhibitor
(enalapril 2.5 20mg/day (uptitrated as
tolerated)
Placebo
8 ACE inhibitor
(enalapril 2.5 20mg/day (uptitrated as
tolerated)
Placebo
9 ACE inhibitor
and
indapamide
(perindopril
4mg/day and
idapamide
2.5mg/day)
10 Angiotensin
Placebo
Patients with
mild to
moderate heart
failure
NYHA II – III
LVEF
≤ 0.35
Patients
with
asymptomatic
heart failure
NYHA I
LVEF ≤ 0.35
Patients who
had a history of
stroke or TIA in
the last 5 years.
Prevent one
death (all cause)
55
months
21
98
Mean age of patients was 61 years. Approximately 80% were
male 4
Treatment also reduced hospital admissions for heart failure
Prevent one
death (all cause)
Prevent one
stroke
34
months
(mean
followup)
88
3.9 years
(mean
followup)
17
251
Mean age of enrolled patients was 60 years5
Treatment reduced the incidence of congestive heart failure
and related hospital admissions
68
Mean age of patients was approximately 64 years 6
70% of patients in the trial had ischaemic stroke
There were similar reductions in the risk of stroke in
hypertensive v. non-hypertensive patients
Patients
Prevent one of a 56
55
258
Mean age of patients was approx. 67 years 7
II receptor
intolerant of
composite of
months
antagonist
ACE Inhibitors
cardiovascular
(median
Death rate (of any cause) was higher in treatment group than
(telmistartan
with
death, MI or
followplacebo group. When hospitalisations for cardiac failure were
80mg/day)
established
stroke
up)
added to the composite endpoint as a primary outcome, the
CVD:
results were non-significant. Study concluded that telmisartan
CHD, PAD or
did not significantly reduce cardiovascular death
cerebrovascular
disease, or DM
with end organ
4.
The SOLVD Investigators. Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. 1991; 325(5): 293-302
damage
5.
The SOLVD Investigators. Effect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions. The New England
Patients
Journal of Medicine. 1992; 327 (10): 685
– 691 with
6.
heart
failure
PROGRESS Collaborative Group. Randomised
trial of a perindopril-based blood-pressure lowering regimen among 6105 individuals with previous stroke or transient ischaemic attack. The
were
excluded.
Lancet. 2001; 358: 1033-42
Placebo
7.
Yusuf S, Teo K, Anderson C, Pogue J, Dyal L, Copland I et al. Telmisartan Randomised Assessment Study in ACE intolerant subjects with cardiovascular disease (TRANSCEND) Investigators.
Effects of the angiotensin-receptor blocker telmisartan on cardiovascular events in high-risk patients intolerant to angiotensin-converting enzyme inhibitors: a randomised controlled trial. The
Lancet. 2008; 372: 1174-1183
20
11 Angiotensin
II receptor
antagonist
(candesartan
4-32mg/day)
Placebo
Patients with
intolerance to
ACE inhibitors
with
symptomatic
heart failure
NYHA II-IV
LVEF ≤ 0.4
12 Betablocker
(bisoprolol
titrated to
target dose of
10mg/day )
Placebo
13 Betablocker
(carvedilol
titrated to
target dose of
25mg twice
daily)
Placebo
Patients with
moderate to
severe heart
failure
Prevent one
death
(cardiovascular
cause) or
hospital
Prevent one
admission for
death
chronic heart
failure
33.7
months
Prevent one
death (all cause)
1.3 years
(mean
followup)
14
40
Patients were already taking other drugs as part of therapy
for heart failure
34
94
18
24
NYHA IV
LVEF < 0.25
(despite
appropriate
conventional
therapy)
Approximately 70% had heart failure of ischaemic cause
Mean age of patients was 61 years 9
83% of which were NHYA III
Current treatment had to include a diuretic and an ACE
inhibitor although other vasodilators were allowed if patients
were intolerant of ACE inhibitors. 96% of patients were on
ACE inhibitors
NYHA III-IV
LVEF ≤ 0.35
Patients with
severe heart
failure
Mean age of enrolled patients was approximately 66 years 8
Prevent one
death (all cause)
10.4
months
(mean
followup)
18
16
Mean age of patients was 63 years 10
Conventional therapy included diuretics and an ACEI or ARB.
97% of patients were already on an ACE inhibitor or ARB
8.
Granger C, McMurray J, Yusuf S, Held P, Michelson E. Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function intolerant to angiotensinconverting enzyme inhibitors: the CHARM-Alternative trial. The Lancet. 2003; 362: 772-776
9.
CIBIS-II Investigators or Committees. The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): a randomised trial. The Lancet. 1999; 353: 9-13.
10.
Packer M, Coats A, Fowler M, Katus H, Krum H et al. Effect of carvedilol on survival in severe chronic heart failure. New England Journal of Medicine. 2001; 344 (22): 1651-1658
21
14 Betablocker
(Metoprolol
modifiedrelease titrated
to a target
dose of
200mg/day)
Placebo
15 Betablocker
(nebivolol
titrated to a
target dose of
10mg/day)
Placebo
16
Spironolactone
25mg daily
Placebo
Patients with
mild to severe
heart failure
Prevent one
death (all cause)
NYHA II – IV
LVEF ≤ 0.40
(despite
optimum
standard
therapy)
28
28
Mean age of patients was 64 years 11
Optimum standard therapy was defined as any combination
of ACE inhibitors, ARB and diuretics
97% of patients were on an ACE inhibitor or ARB
Patients >70
years old with
mild-severe
heart failure
(NYHA I-IV)
irrespective of
LVEF.
Prevent one
death (all cause)
Patients with
heart failure
Prevent one
death (all cause)
Patients had
NYHA Class IV
heart failure in
the 6 months
prior to
enrolment, but
were NYHA class
III or IV at
enrolment.
12
months
(mean
followup)
21
months
(mean
followup)
44
78
Median age of patients was 75 years 12
64% of patients had a LVEF of </=0.35. >95% of enrolled
patients were NYHA class II or III
>87% were already taking an ACE inhibitor or Angiotensin
receptor blocker
24
months
(mean
followup)
9
18
The mean age of patients was 65 years 13
Spironolactone also reduced the frequency of hospitalisation
for heart failure and produced a significant improvement in
the symptoms of heart failure
Patients in the trial were on an ACE inhibitor (if tolerated) and
a diuretic. 10% of patients were also on a beta-blocker
11.
Merit H-F Study Group. Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised intervention Trial in Congestive Heart Failure (MERIT-HF). The Lancet. 1999; 353:
2001-2006
12.
Flather M, Shibata M, Coats A, Van Velhuisen D, Parkhomenko A. Randomised trial to determine the effect of nebivolol on mortality and cardiovascular hospital admission in elderly patients
with heart failure (SENIORS). European Heart Journal. 2005; 26: 215-225.
22
CEREBROVASCULAR/ CARDIOVASCULAR DISEASE
17 Warfarin
( target INR 2 3)
18 Aspirin
19 Aspirin or
other
antiplatelet
Aspirin
75mg daily
Placebo or no
treatment
Placebo or no
treatment
Age > 75yrs with
AF
Primary
prevention of
CVD
Individuals
without history
of occlusive
disease
Secondary
prevention of
CVD in patients
with history of
stroke or TIA
(outwith acute
period)
1st occurrence
of fatal or non
fatal disabling
stroke
(ischaemic or
haemorrhagic),
other
intracranial
haemorrhage or
clinicallyvascular
Serious
significant
event (Defined
arterial
as
MI, stroke or
embolismdeath)
vascular
2.7 years
(mean
followup)
20
5.8 years
(mean
followup)
246
Serious vascular
event (Defined
as non-fatal MI,
non-fatal stroke
or vascular
death)
29-31
months
28-40
54
Mean age of patients prescribed warfarin was 81.5 years 14
73% of patients had a CHADS2 score of 1-2
67% of patients on warfarin remained on this treatment for
the complete duration of the trial
1428
Age range in trials was 19-94yrs 15
Patients had hypertension or coronary risk factors without
overt disease
68 – 94
Antiplatelets include aspirin (most widely studied),
clopidogrel, dipyridamole, and other antiplatelets not
commonly used in UK practice 16 17
13.
Pitt B, Zannad F, Remme W, Cody R, Castaigne W et al. The Effect of Spironolactone on Morbidity and Mortality in Patients with Severe Heart Failure. The New England Journal of Medicine.
1999; 341(10): 709-717
14
.Warfarin versus aspirin for stroke prevention in an elderly community population with atrial fibrillation ( the Birmingham Atrial Fibrillation Treatment of the Aged Study, BAFTA) : a
randomised controlled trial. Lancet 2007; 370: 493 - 503
15
. ATT Collaboration. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet 2009; 373:
1849-60.
23
20 Antiplatelet
21 Aspirin &
dipyridamole
Placebo or no
treatment
Placebo
Secondary
prevention in
patients at high
risk of
cardiovascular
events
Included
patients with
previous MI,
acute MI,
previous
stroke/TIA, and
other high risk
(excluding
acute
stroke)
Secondary
prevention of
CVD in patients
with arterial
vascular
disease:
(Defined as:
coronary
artery disease,
MI, angina,
retinopathy,
nephropathy,
Serious vascular
event (Defined
as non-fatal MI,
non-fatal stroke
or vascular
death)
26
months
15
32
Antiplatelets include aspirin (most widely studied),
clopidogrel, dipyridamole, and other antiplatelets not
commonly used in UK practice 18
Vascular event.
(Defined as
vascular death,
non-fatal stroke
or non-fatal
myocardial
infarction)
30
months
25
163
Mean age of patients 54 years 19
16
. Antithrombotic trialists collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, MI and stroke in high risk patients. BMJ 2002;358:71-86
McGrath E et al. Validity of composite outcomes in meta-analyses of stroke prevention trials: the case of aspirin. Cerebrovascular Diseases 2011; 32(1):22-7.
18.
Antithrombotic trialists collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, MI and stroke in high risk patients. BMJ 2002;358:71-86
19.
The Cochrane Collaboration. Dipyridamole for preventing stroke and other vascular events in patients with vascular disease. The Cochrane Library 2007, Issue 3
17.
24
29
months
50
121
Mean age of patients 55 years 20
22
months
100
184
Mean age of patients was 63yrs 21
22 Aspirin &
dipyridamole
Aspirin
peripheral
arterial disease,
stroke, TIA,
amaurosis
fugax)
23
Thienopyridine
derivative
(Ticlopidine or
clopidogrel)
Aspirin
Secondary
prevention of
CVD in patients
with history of
ischaemic
stroke or TIA
Stroke (all types)
Stroke, MI or
vascular death
28
months
100
223
Secondary
prevention of
CVD
Patients had a
history of
ischaemic or
haemorrhagic
stroke or TIA
Ischaemic or
haemorrhagic
stroke
48
months
100
400-420
Serious vascular
event
41- 44
months
20
68-74
24 Statin
(Simvastatin
40mg daily,
atorvastatin
80mg daily,
pravastatin
40mg daily)
Placebo
Ticlopidine is not available in the UK but has similar mode of
action to clopidogrel
Serious vascular events (non-fatal stroke, non-fatal
myocardial infarction, vascular death) and all-cause mortality
including sudden deaths 22
20
. Dipyridamole for preventing stroke and other vascular events in patients with vascular disease. The Cochrane Library 2007, Issue 3
The Cochrane Collaboration. Thienopyridine derivatives versus aspirin for preventing stroke and other serious vascular events in high vascular risk patients. The Cochrane Library 2009, Issue 4
22.
The Cochrane Collaboration. Interventions in the management of serum lipids for preventing stroke recurrence. The Cochrane Library 2009, Issue 3
21.
25
DIABETES
25 Intensive
sulphonylurea
with insulin to
achieve fasting
plasma
glucose less
than 6.0mmol/
Conventional
treatment
with diet to
aim for fasting
blood glucose
less than
15mmol/l
(Sulphonylurea
s:
chlorpropamid
e,
glibenclamide
or glipizide)
(Metformin
and
sulphonylurea
could be
added or
patients
changed to
insulin if
target not
achieved)
(Insulins:
Ultratard or
Humulin Zn or
isophane
insulin)
Newly
diagnosed type
2 diabetes
patients between 25-65
years
Any diabetes end
point
10 years
(median
duration
of followup)
20
200
Mean age of patients was 54 years 23
Any diabetes-related endpoint was defined as sudden
death, death from hyperglycaemia or hypoglycaemia,
fatal or non-fatal myocardial infarction, angina, heart
failure, stroke, renal failure, digital amputation, vitreous
haemorrhage, retinopathy requiring photocoagulation,
blindness in one eye, or cataract extraction
Diabetes-related death was death due to myocardial
infarction, stroke, peripheral vascular disease, renal
disease, hyperglycaemia or hypoglycaemia, and sudden
death
Median HbA1c over 10 years 7.0% in intensive group
versus 7.9% in conventional group
Diabetes related
death
91
Micro-vascular
complications
36
910
Intensive group had more hypo-glycaemic episodes per
year and higher weight gain than conventional group
Reduction in micro-vascular events were mostly retinal
360
23.
UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients
with type 2 diabetes (UKPDS 33). Lancet 1998; 352: 837-53.
26
DIABETES
Metformin to
achieve fasting
blood glucose
<6.0mmol/l
(maximum
dose 2550mg)
Glibenclamide
was added if
this was not
achieved and if
unsuccessful
changed to
insulin to
achieve fasting
blood glucose
<6.0mmol/l (or
7.0 if on
insulin)
Diet alone to
achieve
fasting blood
glucose
<15mmol/l.
If unsuccessful
sulphonylurea
(chlorpropamide or
glibenclamide)
or metformin
or insulin to
achieve
fasting blood
glucose
<15mmol/l
could be
added
Newly
diagnosed type
2 diabetes
patients between 25-65
years
Any diabetes end
point
10.7
years
(median
followup)
7
80
Mean age of patients was 53 years; mean weight 87kg ;
BMI 31 24
Any diabetes-related endpoint or death was defined as
for the scenario above sudden death, death from
hyperglycaemia or hypoglycaemia, fatal or non-fatal
myocardial infarction, angina, heart failure, stroke, renal
failure, amputation [of at least one digit], vitreous
haemorrhage, retinopathy requiring photocoagulation,
blindness in one eye, or cataract extraction
Overweight
defined as
>120% ideal
body weight
Median HbA1c during 10 years was 7.4% in metformin
group and 8.0% in conventional group
Diabetes related
death
19
203
Microvascular
disease
45
481
Hypoglycaemic episodes were higher in metformin group
compared to diet alone but lower than the sulphonylurea
group. Hypoglycaemia rates increased over time in
insulin group as higher doses were required
24.
UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet.
1998; 352: 854-65
27
DIABETES
26 Intensive
control of
glucose
Included the
addition of
Gliclazide mr
tablets 30120mg daily, to
existing
medication
(which could
also be
adjusted) to
achieve a
glycated
haemoglobin
(HbA1c) value
of 6.5% or less.
Hypoglycaemia
agents chosen
by the
treating
physician
Patients with
type 2 diabetes
mellitus at least
55 years old
with a history of
major macrovascular or
micro-vascular
disease or at
least one other
risk factor for
vascular disease
Major
microvascular or
macrovascular
events (death
from
cardiovascular
causes, nonfatal
myocardial
infarction, or
nonfatal stroke)
Major microvascular events
(new or
worsening
nephropathy or
retinopathy)
5 years
(median
followup)
53
263
Mean HbA1c in control group was 7.3% and intensive
(gliclazide mr) arm was 6.5% after 5 years follow up
Microvascular benefits were mostly due to reduction in
nephropathy 25
No significant effect on major macrovascular events alone
Severe hypoglycaemia occurred in 2.7% of patients on
intensive therapy compared with 1.5% of patients in the
standard therapy group (Number needed to harm =80)
67
333
25.
ADVANCE Collaborative Group, Patel A, MacMahon S, Chalmers J, et al. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008;358:25602572.
28
OSTEOPOROSIS
27
Alendronate
10mg tablets
Placebo
Postmenopausal
women:
Secondary
prevention in
women who had
experienced
previous vertebral
compression
fractures
Rate of
vertebral, nonvertebral or hip
fractures (as
below) over a 5
year period
Vertebral
secondary
prevention
Non-vertebral
secondary
prevention
Hip secondary
prevention
60
months
(5 years)
As per age range
below
As per age range
below
Age range 42-85 but >62 for secondary
prevention
These NNTs apply to the first 5 years of
treatment only
65-69
16
65-69
80
70-74
13
70-74
65
75-79
9
75-79
45
80-84
12
80-84
60
85-89
11
85-89
55
90+
8
90+
40
65-69
52
65-69
260
70-74
39
70-74
195
75-79
36
75-79
180
80-84
27
80-84
135
85-89
24
85-89
120
90+
12
90+
60
65-69
210
65-69
1050
70-74
86
70-74
430
75-79
36
75-79
180
80-84
21
80-84
105
85-89
9
85-89
45
90+
8
90+
40
29
OSTEOPOROSIS
28
Alendronate
Placebo
Postmenopausal
women:
primary
prevention
average T-score
was within 2
standard
deviations of the
mean for bone
density
vertebral
compression
fractures
Rate of
vertebral, nonvertebral or hip
fractures (as
below) over a 5
year period
Vertebral
primary
prevention
Non-vertebral
primary
prevention
Hip primary
prevention
60
months
(5 years)
As per age range
below
As per age range
below
Age range 42-85 but >62 for secondary
prevention
These NNTs apply to the first 5 years of
treatment only.
65-69
148
65-69
740
70-74
123
70-74
615
75-79
67
75-79
335
80-84
97
80-84
485
85-89
89
85-89
445
90+
47
90+
235
65-69
104
65-69
520
70-74
67
70-74
335
75-79
59
75-79
295
80-84
42
80-84
210
85-89
32
85-89
160
90+
12
90+
60
65-69
70-74
236
118
65-69
70-74
1180
590
75-79
50
75-79
250
80-84
27
80-84
135
85-89
11
85-89
55
90+
9
90+
45
All patients received calcium and vitamin D
30
1.3
Tool to assess cumulative risk of drug toxicity and ADRs
The chart below cross-tabulates medication and ADR risks associated with them. It is intended as an
aid to identify actual ADRs or medication safety risks that are the consequence of cumulative ADRs.
For example, if a patient reports constipation, the chart can identify drugs that may contribute to it.
Inversely, the risk of constipation can be anticipated if a patient is taking multiple drugs that may
cause this side effect. Please, note that the list focuses on commonly used drugs and commonly
preventable ADRs, and is not meant to replace more detailed medicines information sources.
Angle closure glaucoma
Serotonin syndrome
Hyperkalaemia
Hypokalaemia
Renal injury
Hypoglycaemia
Respiratory
CV events
Bradycardia
Heart failure
Bleeding
CNS depression
Urinary retention
Constipation
Falls and fractures
ADR
Table 3a: ADR Table
BNF chapter No. - Medication
H2 Blockers 
Laxatives (2)
Loperamide
A
Prochlorperazine etc 
Metoclopramide
Antithrombotics
2
ACEI/ARB
Thiazide diuretics
Loop diuretics
Amiloride/triamterene
Spironolactone
Beta-blocker
CCB (dihydropyridine)
CCB (verapamil/diltiazem)
Nitrates and nicorandil
Digoxin
3
Theophylline
Oral steroids
4
Opiates
Benzodiazepines
D
Sedative antihistamines 
H1 Blockers 
E
Antipsychotics 
SSRI and related
C
TCAs 
MAO inhibitors
5
Antibiotics/antifungals
6
Sulfonylureas, gliptins, glinides
Pioglitazone
7
Urinary antispasmodics
B
Dosulepin 
Alpha blocker
10
NSAIDs
A - STRONG anticholinergics are: dimenhydrinate, scopolamine, dicyclomine, hyoscyamine, propantheline; B STRONG anticholinergics are: tolterodine, oxybutynin, flavoxate; C - STRONG anticholinergics are: amitriptyline,
desipramine, doxepine, imipramine, nortriptyline, trimipramine, protriptyline; D - STRONG anticholinergics are:
promethazine; E - STRONG anticholinergics are: diphenhydramine, clemastine, chlorphenamine, hydroxyzine.
Please see here for full list of anticholinergics! See here for full list of medicines linked to falls.
1
31
2.Case studies: The ‘7 steps’ approach in action
Case 1: Multimorbidity without frailty
Case summary
Patient details
58 year old woman
Current medical history
 Diabetes Type 2 (diagnosed 5 years ago)
 Coronary Heart Disease (NonSTEMI 1 year ago)
 Hypertension
 Atrial Fibrillation
Results




 HbA1c 86 mmol/mol (10%)
 BP 150/85 mmHg
 No urinary protein detected
 eGFR 55ml/min
 BMI 35kg/m2
 PFTs mild
obstruction
COPD
Chronic Back Pain
Depression (2 episodes)
Hypothyroidism
Lifestyle
 Smoking: 10 – 15 cig/d
 Alcohol: 20 units/week
Current Medication
 Aspirin 75mg od
 Metformin 1g tds
 Gliclazide 80mg bd
 Pioglitazone 30mg od
 Salbutamol inhaler prn
 Becotide inhaler 100 bd
 Thyroxine 75 mcg od
Current Function
 Citalopram 20mg od
 Bendroflumethiazide 2.5
mg
 Lisinopril 30mg od
 Amlodipine 10mg od
 Atenolol 50mg od
 Furosemide 40 mg od
 Gabapentin 400mg tds
 Co-codamol 8/500mg 2
tabs up to qds
 Diclofenac 50mg up to
tds
 Omeprazole 40mg bd
Receptionist in local garage. Works 6 half days per week. Provides support for elderly
mother who lives alone and has early dementia. Lives with husband - out of work long
term. Two previous acute admissions to hospital. Flu-like illness leading to exacerbation
of COPD two years ago. Chest pain 12 months ago - found to be in atrial fibrillation on
admission and troponin positive. Angiogram showed widespread coronary artery
disease but not severe enough to warrant revascularisation. Echocardiography showed
normal left ventricular systolic function. On dual aspirin and clopidogrel for 1 year.
Recently moved to aspirin monotherapy.
Most recent consultations
Ongoing problems with ankle swelling. Back pain difficult to manage and resistant to
several strategies. Occasional palpitations, and persistent indigestion with heartburn.
Chronic financial worries. Increasing carer strain.
32
Applying the 7 steps
Checks
1. Therapeutic objectives
 Existing problems
 Prevention
2. Essential drugs
 Essential
replacement function
 Preventing rapid
deterioration
3. (Continued) need for
drugs
 Temporary
indications
 Maintenance doses
 Limited benefit in
general
 Limited benefit in this
patient
4. Therapeutic objectives
achieved?
 Symptom control
 Biochemical/clinical
targets
 Prevention
Medication related risks /problems identified










Secondary prevention of CVD events (incl. stroke prevention in AF)
Rate control in AF
Management of CKD
Management of COPD
Pain control
Management of depression
Control of hypothyroidism
Thyroxine to treat hypothyrodism
Antidiabetic medication to control diabetes
Atenolol is needed for rate control in AF
 Pain control: Is the gabapentin for neuropathic pain (from DM) or
mechanical back pain; co-codamol v paracetamol; NSAID required?
 Duration of antidepressant?
 High dose omeprazole. Active peptic ulcer or oesophagitis? Check
symptoms are of gastric origin rather than angina; may require
endoscopy or trial without NSAID?
 Secondary prevention of coronary events:
- Young and active so potentially a long time to obtain benefit
- Not on statin despite high CVD risk (check if omission or due to
side effects. If side effects, consider alternative statin
- HbA1c high despite 3 antidiabetic drugs; discuss adherence and
HbA1c target
- Check BP control, lipid control and life style
 Stroke prevention in AF:
- CHADS score = 2 - consider replacing aspirin for warfarin
 Rate control in AF: Check pulse
 Management of COPD: Discuss symptom control with patient
 Pain control: Discuss symptom control; gabapentin indicated for
neuropathic pain. Consider withdrawal if not effective or
misprescribed for mechanical back pain. Review efficacy of NSAID
 Management of depression: Discuss symptom control with patient
 Control of hypothyroidism: Recent TFTs?
 Management of CKD: OK at the moment (no proteinuria) but need to
monitor regularly
33
5. Safety
 Drug-disease
interactions
 Drug-drug
interactions
 Monitoring robust?
 ADRs
Risk of ADRs
 Risk of GI bleeding: NSAID + citalopram + aspirin (or warfarin if
changed in step 3)
 Risk of acute kidney injury:
- NSAID + CKD (eGFR 55ml/min). Consider stopping.
- co-prescribed diuretic,ACEI/ARB and NSAID (‘triple whammy’)
- co-prescribed thiazide + loop diuretic. Stop one
- consider more frequent U&Es monitoring
 Risk of CVD/cardiac events:
- NSAID + IHD - diclofenac (ibuprofen and naproxen preferred)
- Pioglitazone [Ankle swelling + ischaemic heart disease]
 Risk of arrythmia: QTc prolongation:
omeprazole/citalopram/gabapentin.
Actual ADRs
 Ankle swelling - due to amlodipine? pioglitazone?
6. Cost-effectiveness
Opportunities for cost minimisation (eg generic substitution) should be
explored
 Secondary CVD prevention: Consider how to prioritise discussions
7. Risks to patient(and allocate time for this in consultation)
adherence
- Most effective intervention would be stopping smoking followed by
 Convenient
Warfarin for AF, BP control, weight reduction, HbA1c control
form/dosing
- Offer and support smoking cessation, diet, exercise
schedule?

COPD
management:
 Technical/cognitive
- Check inhaler technique and inhaler use
ability?
- Adjust dose/formulation if necessary
 Continuity of

Patient
cooperation:
care/CMS beneficial?
- Check this lady is aware of the rationale for medication
 Aligned with patient
- Check this lady is aware of safety advice eg what medication to stop
preferences?
if at risk of dehydration
- Check patients willingness to make lifestyle changes (smoking, diet,
exercise)
 Social support: Impact of stress. Signpost to Alzheimer’s Scotland
helpline (for carers), or self-help for anxiety/ depression
SUMMARY: KEY CONCEPTS IN THIS CASE
1. Large number of medications likely to be needed and effective. High number of medications on
its own not an indicator or problematic prescribing but of high risk patient requiring more support
2. Long medication list making it harder to pick up problems without focused review
3. Potential to usefully detect and treat conditions (in this case AF)
4. Potential for high risk drug combinations particularly in patients on multiple medications
5. Need for direct to patient advice on medication, e.g. regarding dehydration
6. Link with non-pharmacological management
7. Time required in consultation likely to have to be longer than standard to cover the patients
concerns and issues and focus on medication
34
Case 2: Frailty without overt multimorbidity
Case summary
Patient details
69 year old man. Care home resident 2 years. Long term heavy alcohol use in the past. Developed
dementia exacerbated by alcohol related brain damage. Fell at home leading to fractured hip.
Very confused and distressed post surgery. When settled, unable to manage at home post fracture
and transferred to care home. Lacked capacity at time of admission. Rallied and put weight on
initially. Slowly fading over years
Current medical history
 Fracture neck of femur 2 years ago
 Dementia – mixed Alzheimer’s disease / alcohol abuse
Results
 BP 120/84mmHg
 eGFR > 60ml/min
Current Medication [stable since admission]








Trazodone 150mg nocte
Thiamine 50mg tds
Bendroflumethiazide 2.5mg od
Tramadol 50mg qds
Cetirizine 10mg od
Amisulpiride 100mg bd
Diprobase cream as required
Fucibet cream topically bd
Current Function
Assistance of two to transfer to chair. Regular falls as attempts to mobilise unaided. Conversation
confused. Short term memory poor. Prompting required to ensure he eats and drinks. Over the
last 12 months has developed ankle swelling and shortness of breath
35
Applying the 7 steps
Checks
1. Therapeutic objectives
 Existing problems
 Prevention
Outputs
 Increase/prevent further deterioration of ability to self-manage;
ankle swelling; shortness of breath
 Prevent falls/fractures
2. Essential drugs
 Essential replacement
function
 Preventing rapid
deterioration
 None
3. (Continued) need for
drugs
 Temporary indications
 Maintenance doses
 Limited benefit in
general
 Limited benefit in this
patient
 Thiamine - may be redundant if well-nourished in care home.
 Bendroflumethiazide - No longer hypertensive. Potential for
withdrawal
 Tramadol - Indication unclear (may have been started after surgery).
 CNS medication (Trazodone, amisulpride) - Indication unclear.
Consider staged withdrawal if not agitated
 Cetirizine /topicals (Diprobase cream, Fucibet cream).
- Required for itch? Clarify cause (i.e. dermatological versus CNS
problem or drug side effect). If dermatological problem, nonpharmacological measures e.g. attention to washing powder, natural
fabrics, reducing use of perfumed products etc, as well as proper use
of emollients regularly and in sufficient quantity can make a
difference)
 Antimicrobial cream: Use should be limited to short term (e.g. one
week)
4. Therapeutic objectives
achieved?
 Symptom control
 Disease management
 Disease prevention
 Prevent falls/fractures: Possible role for calcium/vitamin D to reduce
falls risk, and for osteoporosis prevention using bisphosphonates or
denosumab
 Ankle swelling and shortness of breath: Consider presence of LVSD.
Potentially highly effective treatment available (ACEI/ARB, BB) if
present. Consider ECG +/ ECHO /BNP
 Ensure thyroid function checked. If deficient treat to replace
5. Safety
 drug-disease
interactions
 drug-drug interactions
 Monitoring robust?
 ADRs
ADR risks
 Risk of CVD events:
- Antipsychotics
 Risk of cognitive deterioration:
- Antipsychotics, antihistamines, tramadol
 Risk of falls/fractures:
- Antipsychotics, antidepressant (sedative), antihistamines
 Risk of serotonin syndrome:
- Tramadol and antidepressant
 Risk of steroid adverse effects (topical and systemic):
- High dose topical steroid
Actual ADRs
 Subacute serotonin syndrome may contribute to confusion
36
6. Cost-effectiveness
7. Risks to patientadherence
 Convenient
form/dosing schedule?
 Technical/cognitive
ability?
 Continuity of care/CMS
beneficial?
 Aligned with patient
preferences?
 Opportunities for cost minimisation (eg generic substitution) should
be explored
 Prevention of falls/fractures
- Decision to start bisphosphonate: Balance ability to take versus
expected benefit. Intravenous bisphosphonate or subcutaneous
denosumab alternative options
 Patient cooperation:
- Involve patient where possible. If deemed to lack capacity, ensure
“Adults with Incapacity Documentation” in place. Discuss with
relevant others e.g. Welfare Guardian, Power of Attorney,
nearest relevant if one exists
KEY CONCEPTS IN THIS CASE
1. Low number of conditions and medications but still high potential for drug related issues
2. Ongoing review of medication commenced for symptomatic relief
3. Apparent low level of multimorbidity but potential for undiagnosed treatable conditions
37
Case 3: Frailty with Multimorbidity
Patient details
87 year old woman
Current medical history
 Cerebrovascular Disease
o Partial anterior circulation stroke 5 years ago
o Vascular Dementia diagnosed 3 years ago
 Hypertension
 Ischaemic Heart Disease
o Atrial Fibrillation 2 years
o MI 15 years ago
 Type 2 Diabetes
 Osteoporosis: Fracture vertebra L2 1 year ago;
T score -3.2 at hip on DXA scan
 Recurrent UTIs
 MMSE 22/30 ACE-R 66/100
 COPD with moderate airflow obstruction
 Hypothyroidism
Results
 BP 106/76 mmHg
 HbA1c 40mmol/mol
 Urine Albumin/Creat ratio: trace microalbuminuria
 Creatinine 124umol/L; eGFR 45ml/min and
stable at this level
 Weight 43kg
Current Medication
 Thyroxine 150mcg once a day
 Alendronate 70mg once a week
 Calcichew D3 forte 1 tab twice a
day
 Metformin 1g TDS
 Gliclazide 160mg bd
 Perindopril 4mg once a day
 Indapamide 2.5mg once a day
 Warfarin as per INR
 Clopidogrel 75mg once a
day
 Atorvastatin 80mg once a
day
 Mirtazapine 30mg nocte
 Zopicolone 7.5mg at night
 Paracetamol 1g QDS
 Omeprazole 20mg once a
day
 Seretide 250 1 puff
twice/day
 Salbutamol as required
 Ipratropium inhaler 4
times/day
 Oxybutinin 5mg bd
 Trimethoprim 200mg once
a day prophylaxis
Current Function
Lives at home with husband who is cognitively intact but limited due to heart failure. Vascular
dementia diagnosed 3 years ago. Steadily worsening memory. Needs regular reorientation by
husband. Marked increase in confusion with infection. Continence a particular issue with multiple
nocturnal trips to toilet. Needs a lot of encouragement to eat and drink enough. Main trips out the
house are to clinics and GP. Speciality hospital clinics.
Most recent consultations
Recent Admissions: Osteoporotic fracture leading to sudden loss mobility one year ago. Delirium in
hospital. Flu-like illness 3 months ago. Admitted with confusion, hypoglycaemia and acute kidney
injury.
38
Applying the 7 steps
Checks
Medication related risks /problems identified
1. Therapeutic objectives
 Existing problems
 Prevention




2. Essential drugs
 Essential replacement
function
 Preventing rapid
deterioration
3. (Continued) need for
drugs
 Temporary
indications
 Maintenance doses
 Limited benefit in
general
 Limited benefit in this
patient
4. Therapeutic objectives
achieved?
 Symptom control
 Biochemical/clinical
targets
 Prevention
5. Safety
 Drug-disease
interactions
 Drug-drug
interactions
 Monitoring robust?
 ADRs
6. Cost-effectiveness
Reduce potential for harms from drugs
Ameliorate effects of dementia
Minimise potential for future episodes of delirium
Maintain physical function and minimise symptoms
 Thyroxine




Huge medication burden
Consider relaxing diabetes, BP and lipid control
Consider continued need for osteoporosis treatment
Review ongoing need for night sedation, antidepressant, PPI and
oxybutynin
 Clopidogrel plus warfarin is rarely indicated
 Thyroxine - Check dose and recent TFTs in case over replaced
 Trimethoprim prophylaxis- no evidence beyond 6 months – see SAPG
 Review evidence for accuracy of UTI diagnoses
 Check INR
 Pursuing surrogate targets (BP, HbA1c, cholesterol) may not be
appropriate in this case
 Symptoms and daily function likely to assume greater importance
 Risk of metformin adverse effects (lactic acidosis)
 Risk of acute kidney injury/lactic acidosis:
o ACEI + diuretic + metformin: Advise patient / carer to stop if
dehydrated
o Renal impairment(eGFR 38 in keeping with Stage 3 CKD; using body
weight, the estimated creatine clearance is 19 ml/min)
 Risk of paracetamol intoxication (max 4g/24 hours paracetamol in
45kg lady). Consider reducing dose or extending dosing interval
 Risk of hypoglycaemia: Tight blood sugar control
o Risk of hypotension/falls: Tight BP control, mirtazapine, zopiclone
 Risk of bleeding events: Combination of warfarin and clopidogrel. Stop
one or other (warfarin is more effective in preventing stroke in AF)
 Anticholinergic effects: Consider oxybutynin having any effect v risk of
increased confusion
 Myalgia: Enquire about statin (high dose) related side effects?
Opportunities for cost minimisation (e.g. generic substitution) should be
explored
39
7. Risks to patientadherence
 Convenient
form/dosing
schedule?
 Technical/cognitive
ability?
 Continuity of
care/CMS beneficial?
 Aligned with patient
preferences?
 COPD management:
- Check inhaler technique and inhaler use
- Adjust dose/formulation if necessary
 Prevention of falls/fractures:
- Verify cognitive/technical ability to take alendronate as intended.
- Consider change to denosumab to aid adherence
 Patient cooperation:
- Ensure patient/carer awareness of likely benefit v burden/adverse
effects
- Consider whether patient has capacity to engage with review
process
- Ensure that carers views and expectations are heard and balanced
against professional advice and patient preferences – especially if
carer has power of attorney
- Discuss effort on both patient and carer in taking medication
- Balance against focussing on nutrition
- Consider narrowing medication to most effective agents
- Ensure that medication review is incorporated into wider
anticipatory care planning discussions
KEY CONCEPTS IN THIS CASE
1. Although most of the medications in this case have a clear indication the cumulative effect is an
enormous drug burden with ‘pernicious’ ADR potential. Careful consideration required to
balance the potential for benefit for this specific patient v a reasonable estimation of life
expectancy
2. Consideration of potential adverse impact of high drug burden on other vital areas e.g. nutrition
3. Strong potential for inadvertent high risk co-prescription on a long drug list
4. Difference in risk between trial populations and frail elderly
5. Likely to have intercurrent illnesses and stressors requiring ‘acute’ / ‘emergency’ therapeutic
review
6. Opportunity costs and potential savings from dispensing / administration /aberrant concordance
through rational prescribing
40
Case 4: Care home resident with multiple morbidity
Patient details
79 year old man
Current medical history
 Stroke 2 years ago
 Dense left hemiparesis
 Cognitive impairment (post CVA)
 Coronary Heart Disease
 Impaired left ventricular systolic function on
ECHO
Results
 BP 160/80
 Continues to smoke 5-10 cigs per day
 U&Es all within normal range
Current Medication





Lansporazole 30mg od
Simvastatin 40mg nocte
Clopidrogel 75mg od
Bisoprolol 2.5mg od
Enalapril 20mg od





Amlodipine 10mg od
Furosemide 40mg od
Trazadone 100mg nocte
Tolteridine MR 4mg nocte
Salbutamol MDI 2 puffs prn
Current Function
Has been in care home for 12 months. Intermittent behavioural upset . Diet and general personal
hygiene improved since been in care home. Shows signs of early dementia and can be difficult to
engage depending on mood.
Most recent consultations
Nursing staff tell you that they have recently requested salbutamol as they think he has asthma as
he’s a little breathless. Persistent issues with peripheral oedema.
41
Applying the 7 steps
Checks
Medication related risks /problems identified
1. Therapeutic objectives
 Existing problems
 Prevention





2. Essential drugs
 Essential replacement function
 Preventing rapid deterioration
 None for essential drug
 The drugs for symptomatic deterioration of HF need to
be titrated for optimal benefit
3. (Continued) need for drugs
 Temporary indications
 Maintenance doses
 Limited benefit in general
 Limited benefit in this patient
 Review need for on-going PPI : If still needed - aim for
dose reduction (maintenance dose is 15mg/day)
 Patient examined and breathlessness due to HF: Stop
salbutamol?
 Trial reduced dose of trazadone
4. Therapeutic objectives achieved?
 Symptom control
 Biochemical/clinical targets
 Prevention
 HF symptoms: Titrate all relevant medicines and monitor
U&E
 Consider options for smoking cessation
5. Safety
 Drug-disease interactions
 Drug-drug interactions
 Monitoring robust?
 ADRs
 Drug-drug interaction: Simvastatin and amlodipine reduce dose of amlodipine as ACE dose is titrated up
 Possible drug-drug interaction with clopidrogel and
lansoprazole
6. Cost-effectiveness
 Opportunities for cost minimisation (e.g. generic
substitution) should be explored
7. Risks to patient-adherence
 Convenient form/dosing schedule?
 Technical/cognitive ability?
 Continuity of care/CMS beneficial?
 Aligned with patient preferences?
 May need support with inhaler and inhaler technique if
continuing treatment
Manage the breathlessness
Manage heart failure (HF)
Manage use of preventative treatments
Minimise medication related harm
Help patient quit smoking
KEY CONCEPTS IN THIS CASE:
1. Low number of conditions and medications but still high potential for drug related issues
2. On-going review of medicines needed for those for symptomatic relief for heart failure
42
3. Hot topics: Further background reading
3.1 Anticholinergics
Why are anticholinergics problematic?
Anticholinergics have long been linked to impaired cognition and falls risk, but (more recently) have
also been linked to increased morbidity and mortality. Anticholinergics may also be a cause of
constipation and urinary retention. The table below shows that anticholinergic effects are dose
dependent (adapted from reference26). Of note is, however, that there is significant inter-individual
variability regarding anticholinergic dose and manifestations of signs and symptoms of toxicity.
Table 4a: Anticholinergic effects
Atropine
dose
equivalent
10 mg
Digestive
tract
5 mg
Decreased
gut
motility
++ Mouth
dryness
2 mg
1 mg
0.5 mg
+ Mouth
dryness
Thirst
Mouth
dryness
Urinary
tract
Skin
Eyes
Cardiovascular
CNS
Red, hot,
dry
+++Mydriasis
+++Blurred
vision
+++
Tachycardia
Fast and weak
pulse
++Mydriasis
++ Tachycardia
Ataxia
Agitation
Delirium
Hallucinations
Delusions
Coma
Restlessness
Fatigue
Headache
+Mydriasis
Blurred
vision
Mydriasis
+ Tachycardia
Palpitations
Urinary
Hot and
retention dry
Tachycardia
Anhidrosis
Drugs with anticholinergic properties continue to be commonly prescribed to older people and those
with mental illness, who are particularly susceptible to adverse effects, even at therapeutic doses. A
recent study in NHS Tayside26 found that use of anticholinergics among older patients had increased
to 24% in 2010, with 7% being classified as carrying a high anticholinergic drug burden.
How to assess and reduce the anticholinergic burden
Not all drugs with anticholinergic properties may individually put patients at risk of severe adverse
effects. However, a wide range of commonly used drugs have anticholinergic properties and their
effects may accumulate. A scale or table that lists the anticholinergic activity of commonly prescribed
drugs can guide clinical decision-making to limit anticholinergic load. One such tool is the
Anticholinergic Risk Scale (ARS), which was developed using 500 most prescribed medications.27 They
ranked medication with anticholinergic potential on a scale of 0–3 (0. limited or none; 1. moderate;
2. strong; 3. very strong potential) based on information available on the dissociation constant for
26
Sumukadas D, McMurdo MET, Mangoni AA, Guthrie B. Temporal trends in anticholinergic medication
prescription in older people: repeated cross-sectional analysis of population prescribing data. Age and Ageing
2014 July 1, 2014;43(4):515-21.
27
Rudolph JL SM, Angelini MC, McGlinchey RE The anticholinergic risk scale and anticholinergic adverse effects
in older persons. Arch Intern Med 2008;168:508-13.
43
the muscarinic receptor and rates of anticholinergic adverse effects, i.e. based on in vitro data which
may not always reflect in vivo effects.28 The scale may not always reflect in vivo actions however.
The ARS has since been modified (subsequently referred to as mARS) to include newer medications
with anticholinergic properties that are available in the United Kingdom (see table overleaf).28
Medications with moderate to severe anticholinergic effects according to other scales
(Anticholinergic Burden Scale29 and Anticholinergic Drug Scale30) were added to the list. Medications
identified as having significant anticholinergic properties in the BNF were also included and
medications not available in the UK were excluded. The table overleaf also lists therapeutic
alternatives with no or minimal anticholinergic effects.
Table 4B: Modified Anticholinergic Risk Scale (mARS)28
mARS category 3
mARS category 2
mARS category 1
Guidance
Desipramine
Trimepramine
Nortriptyline
Clomipramine
Sertraline
Trazodone
Mirtazapine
Paroxetine
Lofepramine
Venlafaxine, duloxetine,
bupropion and trazadone have
low-to-nil systemic
anticholinergic activity
Antidepressants
Amitriptyline
Imipramine
Antipsychotics
Thioridazine
Fluphenazine
Perphenazine
Chlorphenamine
Chlorpromazine
Promethazine
Trifluorperazine
Clozapine
Quetiapine
Doxepine
Risperidone
Olanzapine
Haloperidol
Levomepromazine
Pericyazine
Avoid phenothiazines
Prochlorperazine
Domperidone (antiemetic)
does not penetrate CNS
Among atypical antipsychotics,
aripiprazole and ziprasidone
are the least anticholinergic
Nausea and vertigo
Metoclopramide
Urinary antispasmodics
Oxybutynin
Fesoterodine
Flavoxate
Darifenacin
Trospium
Dosulepin
Solifenacin
Tolterodine
Sedatives
Clemastine
Hydroxyzine
Cyproheptadine
28
Avoid antihistamine sedatives
Sumukadas D, McMurdo MET, Mangoni AA, Guthrie B. Temporal trends in anticholinergic medication
prescription in older people: repeated cross-sectional analysis of population prescribing data. Age and Ageing
2014 July 1, 2014;43(4):515-21.
29
Boustani MA CN, Munger S, Fox C. Impact of anticholinergics on the aging brain: a review and practical
application. Aging Health 2008;4:311-20.
30
Carnahan RM LB, Perry PJ, Pollock BG, Culp KR. The anticholinergic drug scale as a measure of drug-related
anticholinergic burden: associations with serum anticholinergic activity. J Clin Pharmacol 2006;46:1481-6
44
Antiallergics
Cetirizine
Loratadine
Desloratadine may be an
alternative
H2 blockers
Cimetidine
Ranitidine
Amantadine
Levodopa/Carbidopa
Selegeline
Entacapone
Pramipexole
Loperamide
Tiotropium
Pseudoephedrine
Baclofen
Propiverine
Methocarbamol
Reboxetine
PPIs may be an alternative
Antiparkinson
Procyclidine
Benzatropine
Others
Atropine
Dicyclomine
Orphenadrine
Tizanidine
45
3.2 Medication & The Risk of Falls in the Older Person
Reproduced from BHPS at this link
This classification has been based upon a review of the clinical evidence of medicines implicated in
falls and from an analysis of the most commonly used drugs with side effect profiles associated with
an increase in falls risk. The list is not meant to be fully comprehensive but intended to raise
awareness of the types of drugs that can contribute to falls. Drugs have been graded as either a high,
moderate or low risk in terms of their ‘potential to cause falls’.
Highest risk
Guidance
Antidepressants
Avoid tricyclic antidepressants especially with high anti-muscarinic activity e.g.
amitriptyline. SSRIs are associated with a reduced incidence of side effects in the
elderly. Trial of gradual withdrawal should be attempted for all anti-depressants
after 6 –12 months of initial treatment
Antipsychotics
including
atypicals
Risk of hypotension is a dose related effect reduced by the ‘start low go slow
approach.’ Atypical antipsychotics are associated with a similar falls risk than
traditional ones. Attempted withdrawal MUST always be gradual to avoid
precipitation of withdrawal symptoms e.g. rebound agitation, etc. The
phenothiazine prochlorperazine (Stemetil) is frequently inappropriately
prescribed for dizziness due to postural instability and the most frequently
implicated drug causing drug induced Parkinson’s disease
Anti-muscarinic
drugs
(Anticholinergics)
Anti-muscarinic drugs are used in treatment of urinary incontinence and in
Parkinson’s disease. Oxybutynin may cause acute confusional states in the
elderly especially those with pre-existing cognitive impairment
Benzodiazepines
& Hypnotics
Whilst complete withdrawal may not be an achievable goal there is still benefit
to be gained in reducing use to the minimum effective dose. Avoid long acting
benzodiazepines e.g. nitrazepam. Newer hypnotics e.g. zopiclone are associated
with reduced hangover effects but all licensed for short-term use only
Dopaminergics
used in
Parkinson’s
disease
Sudden excessive daytime sleepiness can occur with levodopa and other
dopamine receptor agonists. Careful dose titration is particularly important in
initiation of treatment because of additional risk of inducing confusion. As the
patient ages, maintenance doses may need to be reduced
Moderate risk
Anti-arrhythmics
Dizziness and drowsiness are possible signs of digoxin toxicity – risks of toxicity
are greater in renal impairment or in the presence of hypokalaemia. Flecainide
has a high risk for drug interactions and can also cause dizziness
Anti-epileptics
Group with high risk for potential drug interactions. Important side effects
include: Dizziness, drowsiness and blurred vision (dose related)
Drowsiness and sedation common with initiation of treatment but tolerance to
these side effects is usually seen within 2 weeks of continuous treatment.
Drowsiness and sedation is rare with codeine unless concurrently used in
combination with other drugs with CNS effects. Confusion also reported with
tramadol
Opiate analgesics
Anti-histamines
Somnolence may affect up-to 40% of patients with older antihistamines e.g.
chlorpheniramine. The newer anti-histamines e.g. desloratidine cause less
sedation and psychomotor impairment. Risk of hypotension with cinnarizine is a
46
dose related side effect
Alpha – blockers
Doses used for treatment of BPH less likely to cause hypotension than those
required to treat hypertension
ACEI/ARB
Risk of hypotension is potentiated by concomitant diuretic use. Incidence of
dizziness varies from 4-12% of patients but affects twice as many patients with
heart failure than hypertension
Diuretics
Postural hypotension, dizziness and nocturia are the most frequent problems
seen in the elderly. Diuretics should not be prescribed for long-term use in the
treatment of gravitational oedema
Beta-blockers
Reports of dizziness may be due to postural hypotension and can affect up to
10% of patients. Water-soluble beta-blockers can accumulate in renal
impairment and therefore dose reduction is often necessary
Lower risk
CCBs
Incidence dizziness low especially for once daily dihydropyridine calcium channel
blockers e.g. felodipine
Nitrates
Dizziness may be due to postural hypotension. Advise patient to sit when using
GTN spray or tablets
Oral anti-diabetic
drugs
PPIs & H2
Antagonists
Dizziness due to hypoglycaemia, but usually avoidable. Avoid long acting
sulphonylureas e.g. chlorpropamide.
Avoid cimetidine in polypharmacy patients – high risk of potential drug
interactions. Cimetidine also associated with causing confusion in the elderly.
Reports of dizziness, somnolence are uncommon and mental confusion or
blurred vision rare with the other PPIs and H2 antagonists
47
3.3 Stopping antipsychotics in patients with dementia
Reproduced from QI Hub at this link
Antipsychotic drugs are frequently prescribed with the aim of reducing behavioural and psychological
symptoms of dementia (BPSD) in older people. In Scotland in 2007, 17.7% of people with a diagnosis
of dementia were prescribed an antipsychotic, compared to approximately 12% in 2005–2007 in one
US study. Despite this high rate of use, antipsychotics have only limited benefit in treating BPSD in
older people with dementia and carry significant risk of harm. In 2009, antipsychotics were estimated
to cause approximately 1800 deaths and 1620 cerebrovascular events in people with dementia in the
UK annually. However, clinical trial evidence in nursing home patients with dementia indicates that
chronically prescribed antipsychotic drugs can be safely discontinued in most patients, with longer
term follow-up suggesting a significant reduction in mortality.
Which patients should be prioritised for review?
Patients who have dementia and who have been on antipsychotics for more than 3 months and have
stable symptoms should be reviewed with a view to reducing or stopping antipsychotic medication.
Antipsychotics are associated with an increased risk of falls, delirium, cerebrovascular events and allcause death. Priority groups for reducing antipsychotic medication include:
1. People in care homes: the prescription of antipsychotics for BPSD is most common in these
people, who are also more frail than other populations
2. People with vascular dementia: the risk of cerebrovascular events associated with
antipsychotic medication may be higher in this population
3. People with dementia who also have a history of cardiovascular disease, cerebrovascular
disease or vascular risk factors: The risk of cerebrovascular events associated with
antipsychotic medication may be higher in this population
When should antipsychotic medication NOT be stopped?
Patients who have a co-morbid mental illness that is treated with antipsychotic medication, such as
schizophrenia, persistent delusional disorder, psychotic depression or bipolar affective disorder
should not have antipsychotic medication reduced without specialist advice.
How to reduce antipsychotic medication?
1. As with initiation of medication, reduction should be carried out slowly with monitoring of
effect. Start with a reduction of 25% of the total daily dose. If the current dose is low, e.g. at
the suggested starting dose, the medication may be stopped without tapering the dose
2. Review the effect after one week to assess for: the re-emergence of the initial ‘target’
symptoms. Discontinuation symptoms such as nausea, vomiting, anorexia, diarrhoea,
rhinorrhoea, sweating, myalgia, paraesthesia, insomnia, restlessness, anxiety and agitation.
These symptoms are more common with abrupt withdrawal of antipsychotic medication, and
generally begin within 1 to 4 days of withdrawal and abate within 7 to 14 days
3. If either of the above occurs the clinician should make an assessment of the risks and benefits
of re-instating the previous dose of antipsychotic. Further attempts to reduce the
antipsychotic should be made one month later with smaller decrements, for example 10% of
the total daily dose
4. If there are no particular problems after week 1 then the dose should remain the same with
further review after week 4 (for risperidone and haloperidol) or fortnightly (for Quetiapine).
5. If the reduction has been tolerated without any of the effects described above then reduce
by a further 25% and repeat the process
6. There will be practical issues when reducing the dose, for example the availability and form of
small doses of medication. It is recommended that this is discussed with a pharmacist
7. It is suggested that once the total daily dose is reduced to the recommended starting dose for
the individual antipsychotic, it may be stopped
A best practice guide for optimising treatment and care for behavioural and psychological symptoms
of dementia is also available from Alzheimer’s Society at this link.
48
3.4 Stopping benzodiazepines and z-drugs
Reproduced from NICE at this link.
How do I assess someone who wants to stop benzodiazepines or z-drugs?
- Assess whether this is a suitable time for the person to stop taking the drug (chances of
success are improved when a person's physical and psychological health and personal
circumstances are stable)
- Enquire about:
o Symptoms of depression. Withdrawing these drugs can worsen symptoms of clinical
depression. The priority is to manage depression first, before attempting drug withdrawal
o Symptoms of anxiety Withdrawing treatment when significant symptoms of anxiety are
present is likely to make symptoms worse and is therefore unlikely to succeed. However,
when symptoms are reasonably well controlled and stable it may be possible to attempt
careful drug withdrawal
o Symptoms of long-term insomnia. If insomnia is severe, consider treating this with nondrug treatments prior to starting withdrawal of a benzodiazepine or z-drug
o Any medical problems and whether these are well controlled and stable. If problems are
causing significant distress, consider managing these first, prior to starting withdrawal of
benzodiazepines or z-drugs
o Consider whether the withdrawal of the benzodiazepine or z-drug can be appropriately
managed in primary care (i.e. whether they are willing, committed, and compliant, and
have adequate social support, have no previous history of complicated drug withdrawal and
are able to attend regular reviews
o Consider seeking specialist advice or referral to a specialist centre for people with: A
history of alcohol or other drug use or dependence. Concurrent, severe medical or
psychiatric disorder or personality disorder. A history of drug withdrawal seizures — these
generally occur in people who suddenly stop high doses of the drugs. Slow tapering is
recommended for these individuals
How do I manage someone who wants to stop benzodiazepines or z-drugs?
- Decide if the person can stop their current benzodiazepine or z-drug without changing to
diazepam
- Switching to diazepam is recommended for:
- People using the short-acting potent benzodiazepines (that is, alprazolam and lorazepam)
- People using preparations that do not easily allow for small reductions in dose (that is
alprazolam, flurazepam, loprazolam and lormetazepam)
- People taking temazepam or nitrazepam who choose to withdraw from diazepam after
discussing the advantages and disadvantages
- People experiencing difficulty or who are likely to experience difficulty withdrawing directly
from temazepam, nitrazepam, or z-drugs, due to a high degree of dependency (associated with
long duration of treatment, high doses, and a history of anxiety problems)
- Seek specialist advice (preferably from a hepatic specialist) before switching to diazepam in
people with hepatic dysfunction as diazepam may accumulate to a toxic level in these
individuals. An alternative benzodiazepine without active metabolites (such as oxazepam) may
be preferred
- Negotiate a gradual drug withdrawal schedule (dose tapering) that is flexible. Be guided by
the person in making adjustments so that they remain comfortable with the withdrawal
- Titrate the drug withdrawal according to the severity of withdrawal symptoms
- Drug withdrawal may take 3 months to a year or longer. Some people may be able to withdraw
in less time
- Review frequently, to detect and manage problems early and to provide advice and
encouragement during and after the drug withdrawal
- If they did not succeed on their first attempt, encourage the person to try again
49
- Remind the person that reducing benzodiazepine dosage, even if this falls short of complete
drug withdrawal, can still be beneficial
- If another attempt is considered, reassess the person first, and treat any underlying problems
(such as depression) before trying again
How should I withdraw a benzodiazepine or a z-drug?
- Withdrawal should be gradual (dose tapering, such as 5–10% reduction every 1–2 weeks, or an
eighth of the dose fortnightly, with a slower reduction at lower doses), and titrated according
to the severity of withdrawal symptoms
- This may take 3–4 months to a year or longer. Some people may be able to withdraw in less
time
- For advice on withdrawal, see Advice
- Withdrawal may be undertaken with or without switching to diazepam.
- See Additional information for examples of withdrawal schedules. These should be tailored to
meet individual needs
- For more information on withdrawal schedules for other benzodiazepines and z-drugs, see the
Ashton Manual (available online at www.benzo.org.uk)
Managing withdrawal symptoms
- How should I manage withdrawal symptoms?
- Review frequently to detect and manage problems early, and to provide encouragement and
reassurance during and after drug withdrawal
- Manage anxiety: Explain that anxiety is the most common acute withdrawal symptom
- Reassure that anxiety is likely to be temporary. Consider slowing or suspending withdrawal
until symptoms become manageable. Consider additional use of non-drug treatments
- Adjunct drug therapy should not be routinely prescribed but may be considered: Propranolol:
for severe, physical symptoms of anxiety (such as palpitations, tremor, and sweating) only if
other measures fail
- Antidepressants: only if depression or panic disorder coexist or emerge during drug withdrawal.
- Do not prescribe antipsychotics which may aggravate withdrawal symptoms
- Seek specialist advice if symptoms are severe or difficult to manage
- Manage depression
- If depression emerges or coexists with withdrawal symptoms:
- Consider suspending drug withdrawal until the depression resolves
- See the CKS topic on Depression for further information on the management of depression
- Manage insomnia
What should I advise people undergoing withdrawal?
- Advise that drug withdrawal should be gradual to minimize the risk of withdrawal effects
- Offer reassurance that the person will be in control of the drug withdrawal and that they can
proceed at a rate that suits them. Drug withdrawal may take 3 months to a year or longer if
necessary. Some people may be able to withdraw in less time
- If the person reaches a difficult point in the drug withdrawal schedule, maintain the current
dose for a few weeks if necessary. Try to avoid going backwards and increasing the dosage
again if possible
- Avoid taking extra tablets in times of stress
- Avoid compensating for benzodiazepines or z-drugs by increasing the intake of alcohol or other
drugs (prescription, non-prescription, or illicit drugs) or smoking
- Stopping the last few milligrams is often seen as being particularly difficult
- Reassure the person that this is usually an unfounded fear derived from long-term
psychological dependence on benzodiazepines
- Warn the person not to be tempted to prolong the drug withdrawal to an extremely slow rate
towards the end (such as reducing by 0.25 mg diazepam each month). Advise the person to
consider stopping completely when they reach an appropriate low dose (such as diazepam
1 mg daily)
50
- Give information on withdrawal symptoms
- With slow tapering, many people experience few or no withdrawal symptoms
- If withdrawal symptoms are present with slow tapering, some users will have lost all their
symptoms by the end of the drug withdrawal schedule. For most people, symptoms will
disappear within a few months
- Only a very small number of people will suffer from protracted withdrawal symptoms which
will gradually improve over a year or longer
- Inform the person that nearly all the acute symptoms of withdrawal are those of anxiety
- Explain that some of the withdrawal symptoms may be similar to the original complaint and do
not indicate a return of this
- It is not possible to estimate the severity and duration of withdrawal symptoms as these will
depend on a number of factors (such as severity of dependence and speed of withdrawal)
- For information on managing withdrawal symptoms, see Managing withdrawal symptoms
What if someone does not want to stop taking benzodiazepines or z-drugs?
- Do not pressurize the person to stop if they are not motivated to do so
- Listen to the person, and address any concerns they have about stopping
- Explain that for most people who withdraw from treatment slowly, symptoms are mild and can
usually be effectively managed by other means
- Reassure the person that they will be in control of the drug withdrawal and that they can
proceed at a suitable rate
- Discuss the benefits of stopping the drug. The discussion should include an explanation of
tolerance, adverse effects, and the risks of continuing the drug. See Reasons for stopping for
further information
- Review at a later date if appropriate, and reassess the person's motivation to stop
- In people who remain concerned about stopping treatment despite explanation and
reassurance, persuading them to try a small reduction in dose may help them realize that their
concerns are unfounded
51
3.5 Management of constipation
Reproduced from NICE at this link.
What drugs commonly cause constipation in adults?
-
Many drugs are constipating. The most common are:
Aluminium antacids
Antimuscarinics (such as procyclidine, oxybutynin)
Antidepressants (most commonly tricyclic antidepressants, but others may cause constipation in
some individuals)
- Some antiepileptics (for example carbamazepine, gabapentin, oxcarbazepine, pregabalin,
phenytoin)
- Sedating antihistamines
- Antipsychotics
- Antispasmodics (such as dicycloverine, hyoscine)
- Calcium supplements
- Diuretics
- Iron supplements
- Opioids
- Verapamil
How should chronic constipation be treated in adults?
- Begin by relieving faecal loading/impaction, if present
- Set realistic expectations for the results of treatment of chronic constipation
- Advise people about lifestyle measures — increasing dietary fibre (including the importance of
regular meals), drinking an adequate fluid intake, and exercise
- Adjust any constipating medication, if possible
Laxatives are recommended:
- If lifestyle measures are insufficient, or whilst waiting for them to take effect
- For people taking a constipating drug that cannot be stopped
- For people with other secondary causes of constipation
- As 'rescue' medicines for episodes of faecal loading
If laxative treatment is indicated:
- Start treatment with a bulk-forming laxative
- It is important to maintain good hydration when taking bulk-forming laxatives. This may be difficult
in the elderly
- If stools remain hard, add or switch to an osmotic laxative (use macrogols as first choice of an
osmotic laxative and lactulose if macrogols are not effective, or not tolerated)
- If stools are soft but the person still finds them difficult to pass or complains of inadequate
emptying, add a stimulant laxative
- Adjust the dose, choice, and combination of laxative according to symptoms, speed with which
relief is required, response to treatment, and individual preference
- The dose of laxative should be gradually titrated upwards (or downwards) to produce one or two
soft, formed stools per day
- If at least two laxatives (from different classes) have been tried at the highest tolerated
recommended doses for at least 6 months, consider the use of 5-HT4-receptor agonist or guanylate
cyclase-C receptor agonist as per their recommended place in therapy
- Before prescribing, ensure National Institute for Health and Care Excellence criteria are fulfilled
If the person has opioid-induced constipation:
- Advise them to increase the intake of fluid and fruit and vegetables if necessary
- Avoid bulk-forming laxatives
- Use an osmotic laxative and a stimulant laxative
- Adjust the laxative dose to optimize the response
- More information on the pros and cons of the various laxatives, is available here
52
3.6 Management of blood glucose control- effects of intensifying control
Reproduced from QI hub at this link.
See this link for diabetes prescribing strategy
What is the optimal level of blood glucose control?
Intensive blood glucose control can have benefits in reducing microvascular events, but four key
randomised controlled trials (UKPDS 33, ACCORD, ADVANCE and VAT) also show that this is at the
cost of increases in hypoglycaemia (increase 42 events per 1000 treated patients over 4.4 years ( CI
25.8-61.7) ). The figure below shows that an HbA1c level of 7.5% is associated with lowest all-cause
mortality. In nearly 48,000 primary care patients who had stepped up their hypoglycaemic
treatment, risk of death rose significantly on both sides of the reference group achieving this
reference level. The patient subgroup with the lowest HbA1c levels (median HbA1c of 6.4%) had a
1.52 (1.32 to 1.76) fold increased risk of death and the patient subgroup with the highest HbA1c
levels (median 10.5%) had a 1.79 (1.56 to 2.06) –fold increased risk of death.
What are the implications for clinical practice?
The observational nature of the above cited study implies that causes of death other than
hypoglycaemia may not have been completely controlled for. However, older people were identified
as being at greatest risk. These results are of particular concern for the frailer groups of patients, who
given the long lead time to obtain any supposed benefits from low HbA1c, may nonetheless suffer
adverse outcomes. In addition, patients who suffer from hypoglycaemia are at increased risk of falls.
[Survival as a function of HbA1c in people with type 2 diabetes: a retrospective cohort study The
Lancet, 2010 Volume 375, Issue 9713, Pages 481-489C. Currie, et al.]
53
Appendix A: General Medication Review leaflet
The below patient information leaflet is available for download from this link, created by NHS
Highland.
54
Appendix B: Sick Day Rules: Information for healthcare
professionals and patients
The following guidance documents for health professionals and patients are available for download,
created by NHS Highland.
Health Professionals Guidance (below) is available at this link
55
Patient guidance (below) is available at this link
56
Appendix C: NNT and the Methodology for NNT used
Inclusion of Number Needed to Treat Data in the Scottish Government
Polypharmacy Guidance
Standard Operating Procedure (SOP)
1. Background
The Scottish Government Polypharmacy Guidance 2015 is intended as a practical tool to help
prescribers decide when it is appropriate to initiate and continue long-term medicines, especially in
the management of long term conditions. In some circumstances, and in consultation with the
patient, it may be appropriate to discontinue treatments. Presentation of numbers needed to treat
(NNT) for a range of medicines is one tool that prescribers may use to aid discussions with patients
about the likely benefit.
The NNT is defined as the expected number of people who need to receive the experimental rather
than the comparator intervention for one additional person to either incur or avoid an event in a
given time frame. An NNT of 10 can be interpreted that one additional (or less) person will incur an
event for every 10 participants receiving the experimental intervention rather than control over a
given time frame.
2. Scope
This SOP is intended to describe the roles of the Association of Scottish Medicines Information
Pharmacists (ASMIP) in the development and maintenance of the NNTs and to describe a systematic
approach to their calculation.
3. Defining NNTs
3.1 Defining the medicine/ intervention and the clinical outcome of relevance
The medicines used in the first edition of the Scottish Government Polypharmacy Guidance 2012
should be included. These will be reviewed to ensure that they are both specific and
measurable. Consideration also needs to be given to their relevance to clinical practice, e.g. is
the medicine likely to be used in this clinical context and is the comparator described the most
relevant to clinical practice?
3.2 Identifying relevant medical literature
The following principles should be applied:
 Cochrane reviews where available should be used
 Systematic reviews should generally be used in preference to individual randomised
controlled clinical trials (RCT), unless the RCT includes a greater number of patients than
a corresponding systematic review
 Where systematic reviews are not available individual randomised controlled trials may
be used
The MI pharmacist should carry out a standard Medline® or Embase® search using relevant
Medical Subject Heading (MeSH) terms and Boolean operators. In particular the following
should be identified:
 Cochrane systematic reviews
 Other high quality systematic reviews
 Pivotal trials for the medicine in the relevant indication
Ideally studies should be identified from the previous five years, but in exceptional
circumstances, e.g. where only a single pivotal trial has been published, or no newer systematic
reviews have been published, older clinical trials or systematic reviews may be used.
3.3 Dealing with multiple trials/ meta-analyses
Where more than one review or trial is identified for the relevant indication and intervention
the following criteria should be assessed:
57
 Relevance to the defined medicine/ intervention
 Size of the study or review
 Similarity of review/ study cohort to the Scottish population
A judgement can then be made, using the criteria above to identify the most relevant trial or
review from which the NNT can be calculated. Where the studies are very similar, the NNT
should be calculated for each individual study and the mean taken for inclusion in the table.
4. Calculating NNTs
The NNT can be calculated from the absolute risk reduction (ARR) taken from a clinical trial or
systematic review. ARR = p1- p2 , where p1 is the baseline or placebo rate and p2 is response rate in
the intervention group in a clinical trial. The NNT can be calculated as 1/ (p1-p2).31 Where the benefit
is accrued over a number of years, the annual NNT can be calculated by dividing the NNT by the
number of years over which the study was conducted.
5. Recording research
The MiDatabank® project management function should be used to record all research. The following
information should be recorded:
 The literature search
 Trials/ reviews identified
 Absolute risk reduction figures taken from the study(ies)
 The calculation used to define the NNT
6. Presenting the of NNT data
All NNT data should be tabulated to include the following:
 Intervention - the medicine or other intervention of interest
 The comparator
 Outcome - the desired outcome from the proposed treatment
 NNT - calculated using standard methodology
 Duration of study/ intervention
 Demographics of population - age, sex (where relevant), co-morbidities
 Reference - main reference used to calculate the NNT
7. Referencing
Vancouver style should be used to reference all trials/ reviews used in the calculation of NNTs.
Where data has been taken from websites, the web address and the date accessed should be
recorded.
8. Checking/ Peer Review
A peer check should be undertaken by another MI or clinical pharmacist prior to publication. The
check should include:
 Clarity and completeness
 Any obvious gaps in the information concerning the patient demographics
 A calculation check for the NNT
31
Hutton JL. Number needed to treat and number needed to harm are not the best way to report and assess
the results of randomised clinical trials. Br J Haematol 2009;146
58
Appendix D: Health Economics Analysis of
Polypharmacy reviews
Expected health economic impacts 2015
Polypharmacy reviews can be expected to deliver long-term direct and indirect economic benefits. A
direct reduction in the cost of medicines prescribed, and reduction in the waste of medicines is
anticipated. In terms of indirect economic benefits, a patient stabilised on fewer medicines will
potentially require less contact with health professionals, thereby freeing up healthcare capacity. Of
prime aim is the indirect economic benefit of fewer unscheduled hospital admissions due to adverse
drug reactions.
Scottish SPARRA population groups
Table 5a below summarises the number of patients in the key target group of 75 years and older, in
Scotland, receiving medicines from 10 or more BNF sections, and at risk levels of between 40% and
60%, as identified by the Scottish Patients at Risk of Readmission and Admission (SPARRA) database.
Additionally, the number of patients aged 50 years and older in a care home at any risk level and any
number of BNF sections is also given. The overall total for these two groups is 64,729 (accounting for
some overlap across the two groups).
Table 5a: Target SPARRA1 population
Age 75+
Number of patients
with high
in a
risk
care
3
4
medicines home
2
SPARRA risk score
BNF sections
40%-60%
10+BNF
Total
40,585
39,593
6,861
Age 50+
with high with
5
risk
dementia
medicines
and in a
care home
6,621
6,898
in a care
home,
any risk,
4
any BNF
30,765
1
SPARRA Version 3 estimates the risk of emergency admission in the next 12 months for approximately 3.6m
individuals aged 16 years and older. For the September 2014 release, this is the risk of emergency admission in
st
st
the period 1 September 2014 to 31 August 2015
2
The number of different BNF sections from which a patient’s drugs were prescribed and dispensed. SPARRA
Version 3 uses the most recent 12 months prescribing data available prior to the start of the risk year.
3
Defined as medications in any of the following BNF Sections: 2.1, 2.2, 2.4, 2.5, 2.8, 2.9, 4.1, 4.2, 4.3 and 10.1
4
Identified by a CHI institution code of 93 or 98
5
Evidence of dementia has been determined either by prescribing history (dispensed items within BNF Section
4.11) or previous admission to hospital where diagnosis at discharge includes ICD10 codes (F00-F03, F051); and
ICD9 codes (2900, 2901, 2902, 2904, 2908, 2909).
Cost avoidance – number of drugs stopped
Table 5b below takes these population figures and estimates potential direct savings from stopping
drugs. If one prescribed medication, with an average 6 repeats, and with average unit cost of £9.87
(BNF 2013/14) was stopped for one year, this would equate to about £2.4m avoided cost in the 75+
group. Adding those aged 50+ in care homes to the reviews would give a total of about £3.8m.
Stopping two drugs with 6 repeats would double these estimates to £4.8m and £7.7m respectively
These estimates are consistent with the mid-range of estimates of savings from polypharmacy
reviews in Craig, J (2013). Here, estimates based on surveys of individual health board experiences
ranged from £66 per annum (value of medicine taking ceased), to £155 per annum (made up of: £90
achieved from change in medication; £22 from switching to more cost effective compounds and £43
from cost avoidance measures associated with duplicate prescriptions).
59
Table 5b: Cost avoidance from stopping repeat medication
Cost avoidance £m
assumed
number
of items
stopped
once
assumed
number
of
repeats
stopped
per item
per year
Age 75+
1
Age 50+
with high in a
with high with
5
risk
care
risk
dementia
3
4
medicines home medicines
and in a
care
home
in a care
home,
any risk,
4
any BNF
SPARRA
risk score
BNF
2
sections Total
1
6 40%-60%
10+BNF £2.4
£2.3
£0.4
£0.4
£0.4
£1.8
2
6 40%-60%
10+BNF £4.8
£4.7
£0.8
£0.8
£0.8
£3.6
1
SPARRA Version 3 estimates the risk of emergency admission in the next 12 months for approximately 3.6m individuals
st
aged 16 years and older. For the September 2014 release, this is the risk of emergency admission in the period 1
st
September 2014 to 31 August 2015
2
The number of different BNF sections from which a patient’s drugs were prescribed and dispensed. SPARRA Version 3 uses
the most recent 12 months prescribing data available prior to the start of the risk year.
3
Defined as medications in any of the following BNF Sections: 2.1, 2.2, 2.4, 2.5, 2.8, 2.9, 4.1, 4.2, 4.3 and 10.1
4
Identified by a CHI institution code of 93 or 98
5
Evidence of dementia has been determined either by prescribing history (dispensed items within BNF Section 4.11) or
previous admission to hospital where diagnosis at discharge includes ICD10 codes (F00-F03, F051); and ICD9 codes (2900,
2901, 2902, 2904, 2908, 2909).
Table 5c projects these assumptions onto the given SPARRA populations. Overall savings using the
base-case of £90 per medication stopped gives savings in the range of £3.7m and £5.8m. For the
upper estimate including: medication change; a switching to more cost effective drugs and cost
avoidance measures, the range increases to £6.3m and £10.0m.
Table 5c: Range of estimates of savings from polypharmacy reviews
Unit
Age 75+, 10+ BNF 75+ group plus all
cost/saving sections, SPARRA care home
Scotland
40%-60%
residents
Number of patients with high risk medicines
40,585
Cost estimates based on savings per case p.a
64,729
£m
£m
£9.87
£2.4
£3.8
2 meds stopped; 6 repeats; 1 yr; unit cost £9.87 £9.87
£4.8
£7.7
Lower estimate of value of medicines stopped
£66
£2.7
£4.3
Base-case: change medication only
£90
£3.7
£5.8
£6.3
£10.0
1 med stopped; 6 repeats; 1 yr; unit cost £9.87
Upper estimate: change medication + switching
£155
to cost effective + cost avoidance measures
Indirect impacts – Adverse Drug Reactions
Pirmohamed et al (2004)32 estimate a prevalence of 6.5% (95% C.I. 6.2% to 6.9%) of admissions
judged as being due to an adverse drug reaction (ADR). 80% (78% to 82%) of the ADRs were judged
to have been directly responsible for the admission, while 20% (18% to 22%), although not directly
responsible for the admission, may nevertheless have contributed to it.
32
Pirmohamed M et al. Adverse drug reactions as cause of admission to hospital: prospective analysis of 18,820
patients. BMJ 2004;329:15-19
60
The study determined avoidability of admissions related to an ADR. Only 28% (25% to 30%) of the
ADRs were assessed as unavoidable, while 9% (7% to 10%) were classified as definitely avoidable and
63% (60% to 66%) as possibly avoidable. It was estimated that ADRs were responsible for the death
of 0.15% (0.1% to 0.2%) of all the patients admitted and that patients admitted with an ADR had a
median stay of 8 days (interquartile range 4-18 days).
These ADR attributable fractions and patient risk scores were estimated33 to account for around
16,000 hospital admissions, and a median number of bed days of 128,000 in Scotland. Of these,
about 1,400 ADRs were estimated to be definitely avoidable, and up to 10,000 possibly avoidable. If
these admissions were treated in direct general medicine, the associated estimated cost of bed days
would be around £34.3m of which between £3.1m and £21.6m could be avoidable. The drug cost
associated with polypharmacy was estimated to be between £33m and £55.4m.
To illustrate the associated cost and welfare loss due to loss of life, the Value of Prevented Fatality
(VPF, £1.76m in 2012) was applied to the associated number of deaths, following UK Department for
Transport guidance34 . In Scotland, about 24 fatalities could be attributed to ADRs, with an associated
cost of £35.2m, of which £3.8m was definitely and £26.6m possibly avoidable.
Implementation cost
Table 5d provides an overview of estimated activity and associated costs for reviews in Scotland35.
Total implementation cost will depend on the number of reviews carried out; for the two groups
considered here this might be up to £3.4m and £5.4m respectively, not including wider costs such as
travel. There could be additional efficiencies to be gained if, e.g. multiple reviews are carried out in
one sitting, reducing travel costs, etc.
It should also be stressed that these estimates include the cost of an estimated 15 minutes GP time
dedicated to discussion with the patient. This should not create additional costs to the system as that
time should also be covered under QOF.
Table 5d: Activity and implementation cost
Per patient cost of
polypharmacy review
Estimated average hours and cost,
Scotland
Number of patients with
high risk medicines
Direct cost
Staff
involved
Patient review
Clinical
Pharmacist
Clinical
Discussion between
Pharmacist
pharmacist and GP
GP
Activity
GP discussion with patient
Direct total
On-costs
Total
GP
Age 75+, 10+
BNF sections,
SPARRA 40%60%
75+ group
plus all care
home
residents
40,585
64,729
Total hours
Cost per
allocated
review
1.00 £29
0.25 £7
0.25 £15
£m
£1.2
£0.3
£0.6
£m
£1.9
£0.5
£1.0
0.25 £15
£67
£0.6
£2.7
£1.0
£4.3
£17
£84
£0.7
£3.4
£1.1
£5.4
The review cost is based on: assessment by the pharmacist; consultation with the GP and pharmacist,
and follow-up by the nurse or pharmacist.
33
SG ASDHD (2013) Polypharmacy reviews – cost benefit analysis, Scottish Government, unpublished
http://www.rssb.co.uk/SAFETY/Documents/VPF%20letter%202012%20-%20final.pdf
35
Based on estimates in Craig, J. (2013) Resources, Costs and Benefits Associated with Implementing
Anticipatory Care Plans including Polypharmacy Reviews in Scotland, Scottish Government 2013
http://www.knowledge.scot.nhs.uk/acp-assessment-tool.aspx
34
61
Appendix E: Indicators and monitoring
In parallel with the implementation of National Guidance on medication reviews and polypharmacy,
the Data Working Group of the Polypharmacy Short Life Working Group have been developing a
definition of an indicator of polypharmacy to help monitor trends and the impact of the policy.
The definition of the core indicator is shown in the table below.
ISD Scotland have developed standard reports which can be run by NHS Boards on the national
Prescribing Information System to identify the numbers of patients experiencing polypharmacy
defined in terms of the standard definition. These reports output numbers at the level of NHS Board,
Community Health and Care Partnership and GP Practice. Two versions of the reports are available:
one with the High Risk drug criterion, one without.
Table 6a: Comparison between the standard indicator and the criteria used to identify potential
patients for review (SPARRA listings).
Comparative criteria: SPARRA listings and the standard indicator.
Table 6a
Core definition
SPARRA listing
10 or more BNF sections dispensed in a
single year
Unit of counting
Counting period
Age threshold
BNF section
One year
Listings produced for 75+ and 65-74 on
request
Listings produced regardless of
presence of high-risk: but include
marker indicating dispensing of at least
one high-risk drug
BNF Sections
2.1 Positive inotropic med.
2.2 Diuretics
2.5 Hypertension/heart failure
2.8 Anticoagulants and protamine
2.9 Anti-platelets
4.1 Hypnotics and anxiolytics
4.2 Antipsychotic/antimanic drugs
4.3 Antidepressants
10.1 Rheumatic diseases and gout
Use of high-risk criterion
High risk drugs
Standard Indicator
10 or more BNF paragraphs
dispensed in a 6 month
period with at least one
High Risk drug
BNF paragraph
Six months
Aged 50 and over
At least one high-risk drug
dispensed
See definition of indicator
Box
Specific High Risk Prescribing Indicators.
As described above the definition of standard version of the indicator of polypharmacy contains a
criterion that at least one of the drugs dispensed must be one of a specified list of drugs regarded as
being high risk in themselves.
In addition ISD Scotland has developed a series of standard reports relating to specific high risk drugs
and combinations of drugs.
These reports have been developed following a study called “Protocol for the Effective Feedback to
Improve Primary Care Prescribing Safety (EFIPPS)”, which can be found here. The reports allow
patients to be identified by CHI number within each GP Practice and also identify if any Community
62
Heath and Care Partnership or GP Practice within an NHS Board has a particularly high rate of high
risk prescribing. The reports have integrated links to searches of a practice’s own local systems which
can be used to locate these patients, aiming to improve individual patient safety. The reports are
available for a six quarter trend at GP Practice level, or for the most recent quarter at NHS Board
level.
There are reports for six specific high risk prescribing indicators, as follows:
1. Older person (>=75 years) prescribed an antipsychotic drug
2. Older person (>=65 years) currently taking an ACE inhibitor/Angiotensin Receptor Blocker and a
diuretic, who is prescribed an NSAID (the 'triple whammy')
3. Older person (>=75 years) prescribed an NSAID without gastroprotection
4. Older person (>=65 years) currently taking either aspirin or clopidogrel who is prescribed an NSAID
without gastroprotection
5. Current anticoagulant user prescribed an NSAID without gastroprotection
6. Current anticoagulant user prescribed aspirin or clopidogrel without gastroprotection
For more information, contact ISD Scotland’s prescribing team at NSS.isdprescribing@nhs.net.
SPARRA and the identification of potential patients for medication review.
As preparations were being made for the issuing of national Polypharmacy Guidance in October
2012, it was recognised that the process would be greatly facilitated if lists of potential candidates
for medication review could be generated and distributed to NHS Boards.
Scotland’s principal repository of patient-based information on patterns of dispensing is the
Prescribing Information System which contains detailed information on all prescriptions dispensed in
the community in Scotland. However, the generation and distribution of lists from this system would
have been a major undertaking and would not have been possible in the timescale available.
However a system was available for distributing lists of patients to NHS Boards: SPARRA. The
SPARRA system (Scottish Patients at Risk of Readmission and Admission) is a risk-prediction tool that
calculates the probability that a given patient will be admitted to hospital as an emergency in the
following year based on the patient’s history of hospital admissions and attendances. In addition, in
recent years, a marker, at BNF section level, of drugs dispensed in the previous year has been
incorporated into the SPARRA prediction model. Lists of patients at risk of subsequent hospital
admission are routinely distributed to NHS Boards so that they can be assessed for possible
preventative or anticipatory care.
Hence the SPARRA system provided a means of generating lists of patients who had experienced
polypharmacy in the previous year, at a given level of risk of hospital admission, which could be
distributed to Boards as potential candidates for medication review as described earlier in this
Guidance.
Comparison between SPARRA criteria and the polypharmacy indicator definition.
Hence the use of SPARRA was a pragmatic decision without which potential candidates for
medication review could not have been identified as quickly as they were.
However, the ‘targeting criteria’ involved were dependent upon the information already available as
part of the SPARRA system. This meant that polypharmacy and high-risk drugs could only be
identified at BNF Section level and the only counting period available is one year.
When the Data Working Group set out to define a standard indicator of polypharmacy to facilitate
monitoring and evaluation it was felt that advantage should be taken of the more detailed dispensing
information available on the Prescribing Information System.
However this means that the SPARRA listings and the polypharmacy indicator are based on
different criteria. To avoid potential confusion the two definitions are outlined in the table 6a
above.
It is intended that in future the ability of NHS Boards to derive lists of candidates directly from the
Prescribing Information System will be enhanced. As this method is adopted the same criteria will
increasingly be used for targeting as are used in the indicator of polypharmacy.
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Initial analyses.
The charts below present initial analyses related to the standard indicator. The first shows the
distribution of a simple count of BNF paragraphs by 5 year age group. This analysis does not
incorporate the high-risk drug criterion. The younger age groups, up to the ages of 60 to 70 broadly
speaking, are dominated by individuals who were dispensed either no drugs or drugs from 1 to 4
different BNF paragraphs. In age groups over 70 a majority of individuals are dispensed drugs from 5
or more different BNF paragraphs. However, it can also be seen that age groups below 60 contain
significant numbers and proportions of individuals with high levels of polypharmacy.
The second is directly based on the standard indicator. It shows the proportion of the population
aged 50 and over who satisfy the criteria for the standard indicator – 10 or more BNF paragraphs at
least one of which is a high-risk drug in a six-month period – by five year age group. Overall 13.3% of
the population aged 50 and over meet these indicator criteria. For those aged 80 and above, over a
quarter of the population satisfy the indicator criteria.
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